Infectious Encephalitis Research Articles

Epidemiology of autoimmune encephalitis and comparison to infectious causes-Experience from a tertiary center.

The incidence of autoimmune encephalitis (AIE) has risen in the last decade, yet recent studies are lacking. We compared the epidemiology of autoimmune and infectious encephalitis cases in Tel-Aviv Sourasky Medical Center (TASMC) between 2010 and 2020. All encephalitis cases, aged 18 and above, admitted to TASMC between the years 2010 and 2020 were reviewed for demographic, clinical, laboratory, and imaging data and categorized based on etiology. Two hundred and twenty-five patients with encephalitis were identified. The most common identifiable cause was viral (42%), followed by autoimmune encephalitis (35%), bacterial (18%), and fungal/parasitic (5%). The incidence of AIE cases out of the yearly admitted cases increased substantially, from 3.8/100 K in 2010 to 18.8/100 K in 2020. The incidence of viral cases also increased while those of bacterial and fungal/parasitic infections remained stable. Patients with AIE were younger compared to infectious patients (p-value <0.001) and had lower markers of systemic and cerebrospinal fluid inflammation (p-value for all <0.001). Seizures were more common among AIE patients (p-value <0.001), yet one-year mortality rates were higher among infectious patients (p-value <0.001). AIE incidence has risen significantly in our institution during the past decade, with current rates comparable to those of all infectious causes combined. Based on this cohort, clinical clues for an autoimmune etiology include a non-inflammatory cerebrospinal fluid profile, the presence of seizures, and temporal lobe imaging abnormalities (also common in herpetic encephalitis). In light of its rising incidence and the importance of early treatment, AIE should be considered in the differential diagnosis of all encephalitis cases.

Difficulty in diagnosing intracranial infection caused by Mycobacterium avium in an AIDS patient: case report and review of the literature

BackgroundMycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS).Case presentationA 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests.ConclusionMAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment.

Molecular characterization of Armigeres Subalbatus from Hyderabad region of Telangana state, India.

The mosquito Armigeres subalbatus (Coquillett, 1898) is a significant vector for Japanese encephalitis infection, and breeds in high organic polluted water. Understanding mosquito diversity and there abundance in relation to mosquito-borne diseases is an important component for public health managers. Though the conventional methods for systematic position of mosquito species by using morphological characteristics is a classical method, but it requires perfect expertise and well preserved specimen. Conversely, the molecular analysis of mitochondrial cytochrome C oxidase subunit I (COI) serves as a gene-centric DNA barcoding approach and offers a promising alternative method for mosquito species identification. The study at hand delves into the morphological characteristics of Armigeres subalbatus were compared with COI- gene to ensure a more dependable verification for identification of mosquito species found in Hyderabad region of Telangana. The 489 base pair amplicons were acquired and deposited into the NCBI Gene Bank nucleotide database under the accession number MG686500. The maximum likelihood tree infers that, the Hyderabad species was diverged from USA and Japan species but had ancestral relationship with Tamil Nadu, Karnataka, Maharastra, Kerala and Goa species. Mitochondrial gene (COI) based DNA barcoding is the most reliable and potential alternative technique to identify the mosquito species.

The lipopeptide Pam3CSK4 inhibits Rift Valley fever virus infection and protects from encephalitis.

Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis

BackgroundInfectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy.MethodsHere we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL).ResultsOur pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM.ConclusionsThis study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Anti-LGI1 Autoimmune Encephalitis in a Patient with Rheumatoid Arthritis and MGUS.

Anti-leucine-rich glioma inactivated 1 limbic encephalitis (anti-LGI1 LE) is one of the most frequent autoimmune encephalitis, commonly coexisting with other autoimmune diseases. Rheumatoid arthritis (RA) and monoclonal gammopathy of unknown significance (MGUS) are commonly associated with autoimmune phenomena. However, neither RA nor MGUS have been described in the literature to date as coexisting with anti-LGI1 LE. We present the case of anti-LGI1 LE in a male patient with rheumatoid arthritis, who was also found to have an MGUS. The patient was initially treated with corticosteroids and IV immunoglobulin. After a mild relapse, his treatment was complemented with rituximab, resulting in complete regression of the disease symptoms. Our report provides evidence for the coexistence of anti-LGI1 LE with RA and/or MGUS, thus extending the differential diagnosis of patients suffering with these disease entities that present with neuropsychiatric symptoms suggestive of encephalitis. Moreover, this case raises challenges on the management of the coexistence of these diseases, given the lack of therapeutic guidelines and their potential interaction on a pathophysiological and a clinical level. In a patient with known autoimmune or malignant background who presents with neuropsychiatric symptoms, after excluding infectious encephalitis or central nervous system involvement in the primary disease condition, autoimmune limbic encephalitis (LE) should also be considered.In a patient diagnosed with anti-LGI1 LE there should be an extensive check for coexisting occult pre-malignant conditions, even for months after disease presentation.Clinical management and treatment options of anti-LGI1 LE when coexisting with other autoimmune or pre-malignant conditions can be challenging; thus, more research is needed towards that direction.

First detection of Tetraparvovirus ungulate 1 in diseased cattle (Chinese Simmental) from Hunan province, China

Tetraparvovirus is an emerging parvovirus infecting a variety of mammals and humans, and associated with human diseases including severe acute respiratory infection and acute encephalitis syndrome. In the present study, a Tetraparvovirus ungulate 1 (formerly known as bovine hokovirus) strain HNU-CBY-2023 was identified and characterized from diseased Chinese Simmental from Hunan province, China. The nearly complete genome of HNU-CBY-2023 is 5346 nt in size and showed genomic identities of 85-95.5% to the known Tetraparvovirus ungulate 1 strains from GenBank, indicating a rather genetic variation. Phylogenetic and genetic divergence analyses indicated that Tetraparvovirus ungulate 1 could be divided into two genotypes (I and II), and HNU-CBY-2023 was clustered into genotype II. This study, for the first time, identified Tetraparvovirus ungulate 1 from domestic cattle from mainland China, which will be helpful to understand the prevalence and genetic diversity of Tetraparvovirus ungulate 1.

Role of inflammatory cytokine burst in neuro-invasion of Japanese Encephalitis virus infection: an immunotherapeutic approaches.

Japanese Encephalitis remains a significant global health concern, contributing to millions of deaths annually worldwide. Microglial cells, as key innate immune cells within the central nervous system (CNS), exhibit intricate cellular structures and possess molecular phenotypic plasticity, playing pivotal roles in immune responses during CNS viral infections. Particularly under viral inflammatory conditions, microglial cells orchestrate innate and adaptive immune responses to mitigate viral invasion and dampen inflammatory reactions. This review article comprehensively summarizes the pathophysiology of viral invasion into the CNS and the cellular interactions involved, elucidating the roles of various immune mediators, including pro-inflammatory cytokines, in neuroinflammation. Leveraging this knowledge, strategies for modulating inflammatory responses and attenuating hyperactivation of glial cells to mitigate viral replication within the brain are discussed. Furthermore, current chemotherapeutic and antiviral drugs are examined, elucidating their mechanisms of action against viral replication. This review aims to provide insights into therapeutic interventions for Japanese Encephalitis and related viral infections, ultimately contributing to improved outcomes for affected individuals.

Epidemio-clinical aspects and neuro-meningeal tuberculosis prognosis in Batna

Neuromeningeal tuberculosis is rare, affecting around 1-2% of all tuberculosis cases and 5% of extra pulmonary tuberculosis cases. Our aim is to describe the epidemio-clinical, prognostic and evolutionary aspects of neuromeningeal tuberculosis. Materials and methods: To determine the spectrum of etiological agents of HIV-negative encephalitis and meningoencephalitis in Batna, we conducted a prospective study using an expanded testing approach. Patients were recruited from three departments (intensive care unit, infectious diseases department, pediatrics) during the period from April 1, 2012, to August 31, 2015. Data were collected according to the FLIPS case definition with a standardized form. We sought to identify etiological pathogens following a standardized procedure and to describe the epidemiological, clinical and biological features and outcomes associated with different causes. Results: A total of 141 patients with infectious encephalitis and meningoencephalitis were included in the study. Bacterial etiology was determined in 65/141 (46.1%) of whom 30 cases (21.3%) were of tuberculous origin; 21 confirmed and/or probable cases 9 possible cases with high clinical, epidemiological and radiological probability. The median age was 30.5 (0-83), predominantly female 12/18, 23.3% comorbidity with a frequency of motor deficits (86.7%) and psychiatric disorders (26.8%), respiratory involvement was present in 60% of cases, pleocytosis was present in 22/25 (73.4%). hyperalbuminorachy in 66. 7%, and hypoglycorachia in (46.7%). Anti-tuberculosis treatment was instituted in 90% of cases,17.6% were initially admitted to an intensive care unit, and the median length of hospital stay was 38.5 (1-146). death was identified in 46.6%, with 10% having sequelae. Conclusion: In our study, in addition to viruses, bacteria (especially intracellular) can be responsible for encephalitis and meningoencephalitis, in varying proportions. The most frequent and leading form of bacterial meningoencephalitis in adults is tuberculosis, the prognosis of which depends on early treatment.

Neutrophil extracellular trap-associated protein in cerebrospinal fluid for prognosis evaluation of adult bacterial meningitis: a retrospective case-control study.

Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.

TBE in the Netherlands

Until 2015, tick-borne encephalitis virus (TBEV) was presumed not to be endemic in the Netherlands.1,2 Consequently, the number of diagnostic requests for detection of tick-borne encephalitis (TBE) infection has been low. Between 2006 and 2015, the laboratory of the Netherlands Centre for Infectious Disease Control (CIb), 1 of the 2 laboratories that performed TBEV diagnostics in the Netherlands at the time, received an average of 20 (range 12–27) requests for TBEV diagnostics per year. In the same period, TBE was diagnosed in 7 Dutch patients. All cases were considered to be travel-related. Indeed, 6 out of 7 patients reported that they had recently travelled to TBEV-endemic countries such as Austria (4), Germany (1), and Sweden (1).

Validation of a risk score to differentiate autoimmune and viral encephalitis: a Nationwide Cohort Study in Denmark

BackgroundA score to differentiate autoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to evaluate the performance of the score in a larger and more diagnostically diverse patient cohort.MethodsWe conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015–2022) or autoimmune aetiology (2009–2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC).ResultsA total of 496 patients with encephalitis [AE n = 90, VE n = 287 and presumed infectious encephalitis (PIE) n = 119] were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92–0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84–0.93).ConclusionThe excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.

Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses.

Venezuelan (VEE), eastern (EEE), and western (WEE) equine encephalitis viruses are encephalitic New World alphaviruses that cause periodic epizootic and epidemic outbreaks in horses and humans that may cause severe morbidity and mortality. Currently there are no FDA-licensed vaccines or effective antiviral therapies. Each year, there are a limited number of human cases of encephalitic alphaviruses; thus, licensure of a vaccine or therapeutic would require approval under the FDA animal rule. Approval under the FDA animal rule requires the disease observed in the animal model to recapitulate what is observed in humans. Currently, initial testing of vaccines and therapeutics is performed in the mouse model. Unfortunately, alphavirus disease manifestations in a mouse do not faithfully recapitulate human disease; the VEEV mouse model is lethal whereas in humans VEEV is rarely lethal. In an effort to identify a more appropriate small animal model, we evaluated hamsters in an aerosol exposure model of encephalitic alphavirus infection. The pathology, lethality, and viremia observed in the infected hamsters was inconsistent with what is observed in NHP models and humans. These data suggest that hamsters are not an appropriate model for encephalitic alphaviruses to test vaccines or potential antiviral therapies.

Japanese Encephalitis Virus and Schizophyllum commune Co-Infection in a Harbor Seal in Japan.

The Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has a wide host range, extending from pigs and ardeid birds to opportunistic dead-end hosts, such as humans and horses. However, JEV encephalitis infections in aquatic mammals are rare, with only two cases in seals reported to date. Here, we report a lethal case of JEV and Schizophyllum commune co-infection in an aquarium-housed harbor seal in Japan. We isolated JEV from the brain of the dead seal and characterized its phylogeny and pathogenicity in mice. The virus isolate from the seal was classified as genotype GIb, which aligns with recent Japanese human and mosquito isolates as well as other seal viruses detected in China and Korea, and does not exhibit a unique sequence trait distinct from that of human and mosquito strains. We demonstrated that the seal isolate is pathogenic to mice and causes neuronal symptoms. These data suggest that seals should be considered a susceptible dead-end host for circulating JEV in natural settings.

Forebrain organoids reveal neuronal capacity to elicit protective antiviral responses.

Abstract Mosquito-borne arboviruses with potential to cause neurotropic disease are a global health threat. These neurotropic viruses are the most common cause of infectious encephalitis (inflammation of the brain), yet our knowledge of antiviral immune regulation at this site remains limited. Neurons are the highly targeted by these viruses and thus must be important mediators of viral replication and spread. Our studies sought to use La Crosse Virus, an emerging arbovirus, to define intrinsic neuronal orchestration of antiviral responses between infected cells and neighboring uninfected bystanders. We observed widespread infection and viral growth in both murine cortical neurons and cerebral organoids. Transcriptomics approaches revealed infection of cortical neurons induced expression of interferon-stimulated genes (ISGs) in both infected and bystander neurons. In forebrain organoids, we found that uninfected bystander neurons have high ISG expression as compared with neighboring infected neurons. Intriguingly, this bystander activation was capable of restricting viral spread. This finding demonstrates that intraneuronal communication mediates protective antiviral response in the CNS. Future directions aim to define the mediators of communication and the protective antiviral signatures using spatial transcriptomics of infected organoid sections.

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

Brain on Fire: How Brain Infection and Neuroinflammation Drive Worldwide Epilepsy Burden

Roughly 80% of the global burden of epilepsy resides in low- and middle-income countries (LMICs; WHO, 2022). Despite numerous new therapies for the treatment of epilepsy, the number of patients who remain resistant to available medications is unchanged. Additionally, no therapy has yet been clinically proven to prevent or attenuate the development of epilepsy in at-risk individuals. Unfortunately, access to next generation therapies in LMICs is low, the stigma associated with epilepsy remains high, and access to adequate resources is unchanged. Thus, the global epilepsy burden disproportionately falls on LMICs such that strategies to conscientiously integrate global epilepsy risk factors into preclinical research may meaningfully advance 21st century epilepsy therapies. Brain infections are one of the main risk factors for epilepsy in resource-poor settings. Further, both infection- and autoimmune-associated encephalitis contribute to worldwide epilepsy risk and remain relatively understudied. For example, clinical SARS CoV-2 infection can induce rare instances of encephalopathy and acute seizures. Among viruses known to cause acute brain infection, enteroviruses increase risk for encephalitis-induced epilepsy, but are not associated with risk for other neurodevelopmental disorders (eg, autism spectrum or attentional deficit hyperactivity disorders). Naturally occurring models of viral infection-induced epilepsy therefore provide an exquisite opportunity to uncover novel contributors to epileptogenesis. Moreover, the convergent neuroinflammatory pathways that are associated with viral infection-induced encephalitis and autoimmune encephalitis reflect an untapped therapeutic opportunity to meaningfully reduce the global burden of epilepsy. This review summarizes the latest advances in translational research integrating encephalitis-induced seizure and epilepsy models, in tandem with progress in clinical diagnosis of inflammation and virally mediated epilepsy. This improved awareness of the shared biological underpinnings of epileptogenesis following brain infection or autoimmune encephalitis is anticipated to beneficially impact the global burden of epilepsy.

Identification of Potent and Selective Inhibitors of Acanthamoeba: Structural Insights into Sterol 14α-Demethylase as a Key Drug Target.

Acanthamoeba are free-living pathogenic protozoa that cause blinding keratitis, disseminated infection, and granulomatous amebic encephalitis, which is generally fatal. The development of efficient and safe drugs is a critical unmet need. Acanthamoeba sterol 14α-demethylase (CYP51) is an essential enzyme of the sterol biosynthetic pathway. Repurposing antifungal azoles for amoebic infections has been reported, but their inhibitory effects on Acanthamoeba CYP51 enzymatic activity have not been studied. Here, we report catalytic properties, inhibition, and structural characterization of CYP51 from Acanthamoeba castellanii. The enzyme displays a 100-fold substrate preference for obtusifoliol over lanosterol, supporting the plant-like cycloartenol-based pathway in the pathogen. The strongest inhibition was observed with voriconazole (1 h IC50 0.45 μM), VT1598 (0.25 μM), and VT1161 (0.20 μM). The crystal structures of A. castellanii CYP51 with bound VT1161 (2.24 Å) and without an inhibitor (1.95 Å), presented here, can be used in the development of azole-based scaffolds to achieve optimal amoebicidal effectiveness.

Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model

Alzheimer's disease is classified as a progressive disorder resulting from protein misfolding, also known as proteinopathies. Proteinopathies include synucleinopathies triggered by misfolded amyloid α-synuclein, tauopathies triggered by misfolded tau, and amyloidopathies triggered by misfolded amyloid of which Alzheimer's disease (β-amyloid) is most prevalent. Most neurodegenerative diseases (>90%) are not due to dominantly inherited genetic causes. Instead, it is thought that the risk for disease is a complicated interaction between inherited and environmental risk factors that, with age, drive pathology that ultimately results in neurodegeneration and disease onset. Since it is increasingly appreciated that encephalitic viral infections can have profoundly detrimental neurological consequences long after the acute infection has resolved, we tested the hypothesis that viral encephalitis exacerbates the pathological profile of protein-misfolding diseases. Using a robust, reproducible, and well-characterized mouse model for β-amyloidosis, Tg2576, we studied the contribution of alphavirus-induced encephalitis (TC-83 strain of VEEV to model alphavirus encephalitis viruses) on the progression of neurodegenerative pathology. We longitudinally evaluated neurological, neurobehavioral, and cognitive levels, followed by a post-mortem analysis of brain pathology focusing on neuroinflammation. We found more severe cognitive deficits and brain pathology in Tg2576 mice inoculated with TC-83 than in their mock controls. These data set the groundwork to investigate sporadic Alzheimer's disease and treatment interventions for this infectious disease risk factor.

Balamuthia Amebic Encephalitis Cured and Discharged.

Intracerebral granulomatous infectious encephalitis caused by Baboon Balamuthia amoeba is a rare form of infectious granulomatous amoebic encephalitis. There are very limited case reports of cured discharges. The authors report a 59-year-old male patient who met the diagnostic criteria for granulomatous infection caused by Baboon Balamuthia amoeba. After treatment, the patient's condition improved, and he was discharged from the hospital. The authors reviewed the data of this patient, analyzed relevant imaging information, and summarized our experience to enhance understanding of this condition.