Diagnostic approach to encephalitis and meningoencephalitis in adult returning travellers

Background

Encephalitis and meningoencephalitis are severe, sometime life-threatening infections of the central nervous system. Travellers may be exposed to a variety of neurotropic pathogens.

High-throughput sequencing for the aetiologic identification of viral encephalitis,meningoencephalitis, and meningitis. A narrative review and clinical appraisal

Background

Viral aetiologies are the most common cause of central nervous system (CNS) infections. Approximately one-half of CNS infections remain of undetermined origin. High-throughput sequencing (HTS) brought new perspectives to CNS infection investigations, allowing investigation of viral aetiologies with an unbiased approach. HTS use is still limited to specific clinical situations.

Diagnostic tools for immune causes of encephalitis

Background

Autoimmune encephalitis (AE) refers to a central nervous system (CNS) antibody-mediated entity characterized by a rapid onset behavioural and cognitive decline that can be associated with movement disorders, epileptic and dysautonomic features. Interestingly, it is thought to be as common as its infectious disease counterpart and can share some clinical, radiological, and laboratory findings.

Usefulness of the FilmArray meningitis/encephalitis (M/E) panel for the diagnosis of infectious meningitis and encephalitis in Taiwan

Background/purposeEarly recognition of causative pathogens is critical for the appropriate management of central nervous system infection and improved outcomes. The BioFire^® FilmArray^® Meningitis/Encephalitis Panel (BioFire^® ME Panel, BioFire Diagnostics) is the first U.S. Food and Drug Administration (FDA)-approved multiplex PCR assay that allows the rapid detection of 14 pathogens, including bacteria (n = 6), viruses (n = 7), and fungi (n = 1), from cerebrospinal fluid (CSF). The performance of the panel is expected to be dependent on the epidemiology of M/E in different geographical regions.MethodsIn this preliminary study, we used the BioFire^® ME Panel in 42 subjects who presented to the emergency department with symptoms of M/E in our hospital. The results were compared to conventional culture, antigen detection, PCR, and various laboratory findings.ResultsThe panel detected six positive samples, of which five were viral and one bacterial. We observed an overall agreement rate of 88% between the BioFire^® ME Panel results and the conventional methods. There were no false-positive findings, but five discordant results were observed for enterovirus, herpes simplex virus type 1, Escherichia coli, and Cryptococcus species.ConclusionsThe BioFire^® ME Panel performed equivalently to the traditional PCR methods for virus detection, and better than bacterial cultures. This revolutionary system represents a paradigm shift in the diagnosis of M/E and may aid in the rapid identification of community-acquired M/E. However, the usefulness of this tool is limited in regions with a high prevalence of infectious M/E caused by microorganisms not included in the panel.     

Diagnostic and pathogenetic role of antineutrophil cytoplasmic autoantibodies

Anti-neutrophil cytoplasmic antibodies (ANCA) are mostly known as a useful diagnostic tool in patients with small-vessel vasculitides. With the accumulating knowledge of these autoantibodies, however, it becomes clear that the role of ANCA may not be only limited to a diagnosis of such disorders. The current review addresses, in addition to classical diagnostic associations, other diseases connected with ANCA positivity, both in adults and in children. The etiology of ANCA remains unknown, but still, the importance of both genetic and environmental factors is undoubted. The role of infection and chemicals in the etiology of ANCA-associated diseases is stressed in particular. A pathogenetic role of ANCA is suggested because of clinical observations based on the correlation of the vasculitis activity and the titer of ANCA. Many experiments show the effects of ANCA in various steps of an inflammatory process, particularly on leukocyte microbicidal activity and oxidative burst. Recent findings are analyzed in the experimental field and they are correlated with clinical significance.     

Long-term outcome of acute encephalitis of unknown aetiology in adults

Encephalitis is caused by a variety of conditions, including infections of the brain by a wide range of pathogens. A substantial number of cases of encephalitis defy all attempts at identifying a specific cause. Little is known about the long-term prognosis in patients with encephalitis of unknown aetiology, which complicates their management during the acute illness. To learn more about the prognosis of patients with encephalitis of unknown aetiology, patients in whom no aetiology could be identified were examined in a large, single-centre encephalitis cohort. In addition to analysing the clinical data of the acute illness, surviving patients were assessed by telephone interview a minimum of 2 years after the acute illness by applying a standardized test battery. Of the patients with encephalitis who qualified for inclusion (n = 203), 39 patients (19.2%) had encephalitis of unknown aetiology. The case fatality in these patients was 12.8%. Among the survivors, 53% suffered from various neurological sequelae, most often attention and sensory deficits. Among the features at presentation that were associated with adverse outcome were older age, increased C-reactive protein, coma and a high percentage of polymorphonuclear cells in the cerebrospinal fluid. In conclusion, the outcome in an unselected cohort of patients with encephalitis of unknown aetiology was marked by substantial case fatality and by long-term neurological deficits in approximately one-half of the surviving patients. Certain features on admission predicted an unfavourable outcome.     

Aseptic meningitis in adults and children: Diagnostic and management challenges

BackgroundAseptic meningitis represents a common diagnostic and management dilemma to clinicians.ObjectivesTo compare the clinical epidemiology, diagnostic evaluations, management, and outcomes between adults and children with aseptic meningitis.Study designWe conducted a retrospective study from January 2005 through September 2010 at 9 Memorial Hermann Hospitals in Houston, TX. Patients age ≥ 2 months who presented with community-acquired aseptic meningitis with a CSF white blood cell count >5 cells/mm³ and a negative Gram stain and cultures were enrolled. Patients with a positive cryptococcal antigen, positive blood cultures, intracranial masses, brain abscesses, or encephalitis were excluded.ResultsA total of 509 patients were included; 404 were adults and 105 were children. Adults were most likely to be female, Caucasian, immunosuppressed, have meningeal symptoms (headache, nausea, stiff neck, photophobia) and have a higher CSF protein (P < 0.05). In contrast, children were more likely to have respiratory symptoms, fever, and leukocytosis (P < 0.05). In 410 (81%) patients, the etiologies remained unknown. Adults were more likely to be tested for and to have Herpes simplex virus and West Nile virus while children were more likely to be tested for and to have Enterovirus (P < 0.001). The majority of patients were admitted (96.5%) with children receiving antibiotic therapy more frequently (P < 0.001) and adults receiving more antiviral therapy (P = 0.001). A total of 384 patients (75%) underwent head CT scans and 125 (25%) MRI scans; all were normal except for meningeal enhancement. All patients had a good clinical outcome at discharge.DiscussionAseptic meningitis in adults and children represent a management challenge as etiologies remained unknown for the majority of patients due to underutilization of currently available diagnostic techniques.     

Diagnostic delay of endometriosis in adults and adolescence-current stage of knowledge

PurposeThe purpose of this article is to provide a modern perspective on the diagnosis of endometriosis with particular attention to the role of ultrasound examination. In the present study, we highlight the problem of endometriosis in teenage girls and discuss the patients’ perspective on the diagnostic process.MethodsIn order to present the most recent reports on the diagnosis of endometriosis, the PubMed database was searched. Articles published within the last 3 years (2019–2021) and those considered relevant during the bibliographic review were analyzed.ResultsThe role of ultrasound examination and assessment of patients' perspective related to delayed and incorrect diagnosis were considered to be the most important in the recent reports. Attention was also paid to the problem of endometriosis diagnosis in adolescent girls.ConclusionsAppropriately constructed and used questionnaires help to determine the risk of endometriosis in a particular patient. The primary method for diagnosis is extended ultrasound examination, which should be performed especially in patients with a high risk of developing the disease. This procedure is applicable to both adult and adolescent women. Awareness of the possibility of developing the disease in a particular patient, combined with appropriate use of ultrasound examination, can contribute to the decrease in diagnostic delay.     

Training and assessment of medical specialists in clinical microbiology and infectious diseases in Europe

BackgroundThere is wide variation in the availability and training of specialists in the diagnosis and management of infections across Europe.ObjectivesTo describe and reflect on the current objectives, structure and content of European curricula and examinations for the training and assessment of medical specialists in Clinical (Medical) Microbiology (CM/MM) and Infectious Diseases (ID).SourcesNarrative review of developments over the past two decades and related policy documents and scientific literature.ContentResponsibility for curricula and examinations lies with the European Union of Medical Specialists (UEMS). The ID Section of UEMS was inaugurated in 1997 and the MM Section separated from Laboratory Medicine in 2008. The sections collaborate closely with each other and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Updated European Training Requirements (ETR) were approved for MM in 2017 and ID in 2018. These comprehensive curricula outline the framework for delivery of specialist training and quality control for trainers and training programmes, emphasizing the need for documented, regular formative reviews of progress of trainees. Competencies to be achieved include both specialty-related and generic knowledge, skills and professional behaviours. The indicative length of training is typically 5 years; a year of clinical training is mandated for CM/MM trainees and 6 months of microbiology laboratory training for ID trainees. Each Section is developing examinations using multiple choice questions to test the knowledge base defined in their ETR, to be delivered in 2022 following pilot examinations in 2021.ImplicationsThe revised ETRs and European examinations for medical specialists in CM/MM and ID provide benchmarks for national authorities to adapt or adopt locally. Through harmonization of postgraduate training and assessment, they support the promotion and recognition of high standards of clinical practice and hence improved care for patients throughout Europe, and improved mobility of trainees and specialists.     

Facing the threat of highly infectious diseases in Europe: the need for a networking approach

In recent years emerging and re-emerging infections, as well as the risk of bioterrorist events, have attracted increasing attention from health authorities because of the epidemic potential that renders some of them a real public health challenge. These highly infectious diseases (HIDs) are occurring more and more frequently in Europe, and despite the many initiatives in place to face them, many unsolved problems remain, and coordinated efforts for dealing with HIDs appear mandatory. Whereas uncoordinated measures would lead to only partial and poor responses to these emerging threats, networking represents a valuable approach to these diseases, in order to: (i) ensure a rapid and effective response; (ii) stimulate complementarity and prevent duplication; (iii) promote international cooperation, exchange of experience, good practice and protocols; and (iv) support the less prepared countries in the European Community.     

辽宁省乙脑病毒的分离与鉴定

目的 对2002年辽宁省采集的蚊虫标本进行病毒分离与鉴定。方法 从辽宁省采集蚊虫标本4927只，用细胞培养的方法分离病毒，对新分离的病毒进行血清学（ELISA和IFA方法）、分子生物学鉴定。结果 本实验共研磨蚊虫标本50批，分离到2株病毒，命名为LN02-102、LN02，104。这2株病毒均可致BHK-21细胞病变（CPE）（2—3d），致Vero细胞病变（2—4d），也可致C6／36细胞病变（2—4d）。对3日龄乳鼠2—3d可致死。这2株病毒可与标准乙脑病毒抗体反应。利用病毒PrM区段（基因组456-695核苷酸）进行基因分型分析。新分离的2株病毒属于基因Ⅰ型乙脑病毒。对这2株病毒的E基因区段进行分析，它们之间核苷酸和氨基酸的同源性为100％，与疫苗株SA14-14-2相比，核苷酸差异为4．11％，氨基酸差异在0．60％。结论 在辽宁省采集的蚊虫标本中分离到2株病毒，经血清学和分子生物学鉴定为基因Ⅰ型乙脑病毒，是近年来在辽宁省首次分离到基因Ⅰ型的乙脑病毒。     

Infectious meningitis and encephalitis in adults in Denmark: a prospective nationwide observational cohort study (DASGIB)

ObjectivesTo monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.MethodsNationwide prospective observational study of all cases of proven community-acquired infectious meningitis and encephalitis in adults treated in all infectious diseases departments in Denmark from 1 January 2015 to 30 June 2016. We included data on symptoms, aetiology, treatment and outcome assessed by the Glasgow Outcome Scale (GOS) 30 days after discharge. GOS 1–4 was categorized as unfavourable outcome.ResultsDuring 18 months of observation, we identified 252 cases of viral meningitis (3.6/100 000/year), 214 cases of bacterial meningitis (3.1/100 000/year) and 96 cases of infectious encephalitis (1.4/100 000/year). In bacterial meningitis, Streptococcus pneumoniae was the most frequent infectious agent (n = 101) followed by Staphylococcus aureus (n = 24) and β-haemolytic streptococci (n = 14). Meningococcal meningitis was rare (n = 11). In encephalitis, herpes simplex virus type 1 was most common (n = 37) followed by varicella zoster virus (n = 20), whereas varicella zoster virus (n = 61) was most common in viral meningitis followed by enterovirus (n = 50) and herpes simplex virus type 2 (n = 46). Case fatality and unfavourable outcome occurred in 31/214 (15%) and 96/214 (45%) with bacterial meningitis and in 5/96 (5%) and 55/89 (62%) with encephalitis. For viral meningitis, unfavourable outcome occurred in 41/252 (17%).ConclusionsThe epidemiology and clinical presentation of the examined central nervous system infections differed considerably and bacterial meningitis was more frequent than previously estimated. Overall prognosis remains poor for bacterial meningitis and encephalitis. Prospective nationwide clinical databases of central nervous system infections may be superior to epidemiological monitoring based on notifications or laboratory systems.     

河南省唐河县分离到基因1型乙型脑炎病毒

目的 从河南省唐河县采集的蚊虫标本中分离乙型脑炎病毒(JEV)并确定其基因分型及E基因区段氨基酸序列特征.方法对2004年采集蚊虫标本进行病毒分离,对新分离的乙脑病毒进行生物学、血清学及分子生物学鉴定.逆转录聚合酶链反应(RT-PCR)扩增新分离JEV的PrM、E区段核苷酸序列,测序后应用Clustal X软件做碱基配对分析,MEGA3.1完成病毒进化分析,GENEDOS(3.2)软件完成氨基酸位点分析.结果共采集3722只蚊虫标本,包括:库蚊、骚扰阿蚊、伊蚊及按蚊.从库蚊标本中分离到3株属于基因1型的乙脑病毒,E区段核苷酸和氨基酸与减毒活疫苗株SA14-14-2株的同源性分别为86.9%～87.7%,氨基酸同源性为95.2%～97.0%,存在12处共同的氨基酸位点差异.结论从河南省唐河县首次分离到基因1型的乙脑病毒.E基因与疫苗株相比有部分氨基酸差异,但现行疫苗株理论上可以保护新分离乙脑病毒.     

Patient communication tools to enhance ART adherence counseling in low and high resource settings

Objective

Few articles have examined specific counseling tools used to increase antiretroviral therapy (ART) adherence. We present communication tools used in the context of Project MOTIV8, a randomized clinical trial.

Methods

We developed, piloted, and evaluated pictorial images to communicate the importance of consistent dose timing and the concept of drug resistance. Electronic drug monitoring (EDM) review was also used to provide visual feedback and facilitate problem solving discussions. Adherence knowledge of all participants (n = 204) was assessed at baseline and 48 weeks. Participant satisfaction with counseling was also assessed.

Results

Adherence knowledge did not differ at baseline, however, at 48 weeks, intervention participants demonstrated significantly increased knowledge compared to controls F(1, 172) = 10.76, p = 0.001 (12.4% increase among intervention participants and 1.8% decrease among controls). Counselors reported that the tools were well-received, and 80% of participants felt the counseling helped them adhere to their medications.

Conclusions

Counseling tools were both positively received and effective in increasing ART adherence knowledge among a diverse population.

Practice implications

While developed for research, these counseling tools can be implemented into clinical practice to help patients; particularly those with lower levels of education or limited abstract thinking skills to understand medical concepts related to ART adherence.     

流行性乙型脑炎患者外周血及脑脊液中某些单个核细胞的免疫细胞化学研究

应用单克隆抗体免疫金银染色法检测了１７例经酶联免疫吸附试验确诊的流行性乙型脑炎患者外周血和脑脊液中的乙脑病毒抗原阳性细胞及表达白介素Ⅱ受体、人类白细胞二类抗原和γ－干扰素的单个核细胞。结果提示：（１）该法对乙脑病毒抗原阳性细胞的检测可望成为乙脑早期诊断的新技术；（２）乙脑病毒抗原阳性细胞及白介素Ⅱ受体阳性细胞可作为临床上判断病情和预后的指标；（３）γ干扰素阳性细胞在乙脑患者的脑组织病理损伤过程中可能起重要作用。     

烟台市手足口病合并脑炎病毒分离及基因序列分析

目的 了解烟台地区手足口病合并脑炎病原谱及其基因学特征.方法 采集烟台地区手足口病合并脑炎患者粪便及脑脊液标本,通过细胞培养分离病毒,实时荧光PCR鉴定病毒型别,RT-PCR扩增VP1区基因部分序列并测序,进行序列分析.结果 10份粪便标本分离病毒3株,均为EV71.与C4a型代表株核苷酸同源性为98％～99％,氨基酸同源性98.90％～99.45％.系统发生树中,烟台分离株与C4亚型C4a簇代表株位于同一分支.结论 烟台地区手足口病合并脑炎病原主要为EV71,属于C4亚型C4a簇.     

Fatal amebic encephalitis caused by Balamuthia mandrillaris in an immunocompetent host: a clinicopathological review of pathogenic free-living amebae in human hosts

Encephalitis caused by Balamuthia amebic species is an increasingly recognized chronic granulomatous infectious process that may affect both immunocompetent and immunocompromised individuals. The course of the disease is insidious but fatal in most cases, mainly because of delayed diagnosis, difficulty in isolation and/or identification of the organism, and lack of well-established therapeutic regimens. We report a fatal case of Balamuthia mandrillaris chronic granulomatous encephalitis in an immunocompromised host and review the clinicopathologic characteristics of infections caused by this and other pathogenic free-living amebae.     

2006年山西省运城市成人流行性乙型脑炎临床特征与实验室检验

目的 研究2006年山西省运城市成人流行性乙型脑炎的临床及实验室检验特点,为我国乙脑预防控制提供基础资料.方法对2006年运城市第二人民医院收治的45例乙脑病例进行临床资料分析,对部分中老年患者血清和脑脊液标本进行血清学和分子生物学检测.结果收治入院的45例患者以中老年人为主,其中40岁以上病例占病例总数77.8%(35/45),重型和极重型占病例总数60.0%(27/45),大多数患者合并基础性疾病.研究结果显示,血清乙脑病毒IgM抗体检测为阳性,急性期和恢复期双份血清中和抗体存在4倍以上增高;部分患者脑脊液乙脑病毒核酸检测阳性.结论经实验室特异性检测确认山西省运城市2006年病毒性脑炎为乙型脑炎,病例呈现大年龄组发病特点.     

圣路易斯脑炎病毒样颗粒的真核表达、纯化与鉴定

目的 利用293T细胞表达、纯化圣路易斯脑炎病毒样颗粒（Virus like particles,VLPs）,为研制圣路易斯脑炎病毒免疫诊断试剂奠定基础.方法 构建含圣路易斯脑炎病毒PrM和E基因的重组质粒pcDNA5/FRT-SJME,瞬时转染293T细胞,表达并纯化重组蛋白,通过透射电镜、间接免疫荧光试验、Western-Blot和ELISA对其进行鉴定.结果 表达的重组蛋白形成50 nm的球型颗粒,能与抗圣路易斯脑炎病毒抗体产生特异性反应,与部分黄病毒属阳性血清发生交叉反应.结论 已成功在哺乳动物细胞中表达并纯化了圣路易斯脑炎病毒样颗粒,其具有良好的抗原性和完整的颗粒形态,为进一步研制圣路易斯脑炎病毒感染的免疫诊断试剂奠定了基础.