Detection of encephalitis-causing viruses reveals predominance of chikungunya virus in the state of Bahia, Brazil.

OBJECTIVES: Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis. METHODS: We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants. RESULTS: In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage. CONCLUSION: Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil.

Bovine astrovirus and its role in lymphocytic encephalitis in cattle in Ontario, Canada, 1988-2019.

Astroviruses have been found in cattle and other species with encephalitis. Our objective was to determine the frequency of neurotropic bovine astrovirus (BoAstV) in cases of encephalitis in cattle ≥ 4-mo-old. Of 56 cases of idiopathic lymphocytic encephalitis examined retrospectively (1988-2019), fixed brain from 11 cases (19%) tested positive by semi-quantitative RT-PCR for BoAstV CH13/NeuroS1. None of the control cases tested positive, including 32 with other forms of encephalitis and 40 with no neurologic disease. Most astrovirus-positive cases were 1-2-y-old, with a range of 7 mo to 7 y, and affected both beef and dairy breeds with wide geographic distribution. BoAstV-positive cases had acute onset of neurologic signs of 12 h to 7 d before death or euthanasia. Affected cattle had lymphocytic inflammation throughout the brain including cerebrum, thalamus, midbrain, cerebellum, medulla oblongata, and spinal cord, and affecting gray and white matter. Further PCR testing identified a possible cause in 9 of the 45 (20%) remaining idiopathic cases of lymphocytic encephalitis, including eastern equine encephalitis virus, Listeria monocytogenes, bovine viral diarrhea virus, bovine alphaherpesvirus 1, and ovine gammaherpesvirus 2 (malignant catarrhal fever); we found no cases of infection by West Nile virus, rabies virus, or Chlamydia spp. No cause was identified in 36 of 56 (64%) cases of lymphocytic encephalitis. We frequently identified neurotropic BoAstV in cases of lymphocytic encephalitis that had no previously identified cause. Neurotropic BoAstV infections had gone undetected for decades, but the frequency of BoAstV infections has not increased among contemporary cases.

Susceptibility and cytokine responses of human neuronal cells to multiple circulating EV-A71 genotypes in India.

Enterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia-Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were isolated in India in recent years, no recognizable outbreak of EV-A71 caused HFMD, Acute Flaccid paralysis (AFP) or encephalitis have been reported so far. It is essential to study the pathogenicity or cell tropism of these Indian isolates in order to understand their tendency to cause disease. We investigated the susceptibility and cytokine responses of indigenous EV-A71 genotypes (D and G) isolated from cases of AFP and genotype C viruses isolated from cases of HFMD and encephalitis, in human cells in-vitro. Although all three EV-A71 genotypes could infect and replicate in human muscle and neuronal cells, the genotype D virus showed a delayed response in human neuronal cells. Quantification of cytokine secretion in response to these isolates followed by confirmation with gene expression assays in human neuronal cells revealed significantly higher secretion of pro-inflammatory cytokines TNF-α IL-8, IL-6, IP-10 (p < 0.001) in G genotype infected cells as compared to pathogenic C genotypes whereas the genotype D virus could not induce any of the inflammatory cytokines. These findings will help to better understand the host response to indigenous EV-A71 genotypes for management of future EV-A71 outbreaks in India, if any.

Acute symptomatic seizures and COVID-19: Hospital-based study.

BACKGROUND AND PURPOSE: Post COVID-19 seizures are relatively rare. The aim of the present study was to estimate the frequency of acute symptomatic seizures among patients with COVID-19 and to discuss possible pathophysiological mechanisms. MATERIAL AND METHODS: Out of 439 cases with COVID-19 that were admitted to Assiut and Aswan University hospitals during the period from 1 June to 10 August 2020, 19 patients (4.3 %) presented with acute symptomatic seizures. Each patient underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the brain and conventional electroencephalography (EEG). Laboratory investigations included: blood gases, complete blood picture, serum D-Dimer, Ferritin, C-reactive protein, renal and liver functions, and coagulation profile. RESULTS: Of the 19 patients, 3 had new onset seizures without underlying pathology (0.68 % out of the total 439 patients); 2 others (0.46 %) had previously diagnosed controlled epilepsy with breakthrough seizures. The majority of cases (14 patients, 3.19 %) had primary pathology that could explain the occurrence of seizures: 5 suffered a post COVID-19 stroke (3 ischemic and 2 hemorrhagic stroke); 6 patients had COVID-related encephalitis; 2 patients were old ischemic stroke patients; 1 patient had a brain tumor and developed seizures post COVID-19. CONCLUSION: acute symptomatic seizure is not a rare complication of post COVID-19 infection. Both new onset seizures and seizures secondary to primary brain insult (post COVID encephalitis or recent stroke) were observed.

Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Epidemiology, management, and graft outcomes after West Nile virus encephalitis in kidney transplant recipients.

BACKGROUND: Minimal data exist describing the epidemiology, management, and long-term graft outcomes after West Nile viral disease in kidney transplant recipients (KTRs). METHODS: Single-center observational cohort study of patients who received a kidney transplant between 1/1/1994 and 12/31/2018 and developed WNV at any time point after transplantation. RESULTS: During the 24-year study period, 11 patients had documented WNV infection. Seven patients were recipients of a kidney transplant alone, and four had a simultaneous kidney and pancreas transplant. The mean age at the time of transplant was 44.7 ± 17.1 years, and the mean age at the time of WNV infection was 48 ± 17.2 years. All patients received lymphocyte depleting induction at transplant (alemtuzumab (n = 2), OKT3 (n = 1), or anti-thymocyte globulin (n = 8)). The mean time from transplant to WNV infection was 3.4 ± 5.4 years, and none was suspected of having a donor-derived infection. Three patients were treated for rejection in the 6 months before infection. The most common presenting symptom was altered mental status (n = 7), followed by a combination of fever and headache (n = 4). All patients had detectable serum WNV IgM antibodies at the time of diagnosis. All patients had a reduction in their immunosuppression and received supportive care; only two patients were treated with intravenous immunoglobulins. Nine patients recovered with no residual deficit; however, two suffered permanent neurologic damage. The mean estimated glomerular filtration rate drop at 1 year after the infection was 8.4 ± 13 mL/min/1.73 m2 . Three patients suffered acute rejection within 1 year after the infection episode, likely attributable to aggressive immunosuppressive reduction. The mean follow-up after the infection was 5.1 ± 4.3 years. At last follow-up, two patients lost their kidney allograft, and five patients died. None of the graft losses or deaths occurred within a year of the WNV or were directly attributable to WNV. CONCLUSION: The majority of patients with WNV infection after KTR recovered fully with supportive care and immunosuppressive adjustment without residual neurologic sequelae. Additionally, WNV infection was associated with relatively small reductions in eGFR at 1 year.

Nipah Virus: Past Outbreaks and Future Containment.

Viral outbreaks of varying frequencies and severities have caused panic and havoc across the globe throughout history. Influenza, small pox, measles, and yellow fever reverberated for centuries, causing huge burden for economies. The twenty-first century witnessed the most pathogenic and contagious virus outbreaks of zoonotic origin including severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV) and Nipah virus. Nipah is considered one of the world's deadliest viruses with the heaviest mortality rates in some instances. It is known to cause encephalitis, with cases of acute respiratory distress turning fatal. Various factors contribute to the onset and spread of the virus. All through the infected zone, various strategies to tackle and enhance the surveillance and awareness with greater emphasis on personal hygiene has been formulated. This review discusses the recent outbreaks of Nipah virus in Malaysia, Bangladesh and India, the routes of transmission, prevention and control measures employed along with possible reasons behind the outbreaks, and the precautionary measures to be ensured by private-public undertakings to contain and ensure a lower incidence in the future.

Neurological complications associated with influenza in season 2017/18 in Austria- a retrospective single center study.

BACKGROUND: Neurological complications associated with influenza (NCI) are rare events in adults with seasonal influenza. Information about the characteristics of neurological complications and the burden of disease has been limited to case reports, mainly during the pandemic 2009. Influenza-associated encephalopathy/encephalitis (IAE) is one of the most severe and frequently reported NCI, mostly caused by influenza A. Isolated case reports exist about NCI caused by influenza B. OBJECTIVES: The aim of this single center retrospective study is the better understanding of the frequency and the characteristics of NCI in adults in season 2017-2018, depending on the influenza subtype A or B. STUDY DESIGN: We reviewed 874 adult patients with laboratory confirmed influenza admitted to the Christian Doppler University Hospital Salzburg, Austria from December 2017 until March 2018 looking for NCI. RESULTS: 37 (4 %) of the 874 patients with confirmed influenza had NCI. 4 (11 %) had influenza A and 33 (89 %) had influenza B. IAE was the most frequent complication diagnosed in 24 (65 %) patients, of whom all but one had influenza B and 3 (13 %) had neurological residuals. Moreover 6 (16 %) had isolated epileptic seizures, 2 (5 %) had acute inflammatory demyelinating polyneuropathy (AIDP), and 5 (14 %) were classified as having infection-associated stroke. CONCLUSIONS: We report an incidence of 4 % for NCI and a high frequency of IAE caused by subtype B. Therefore, we recommend considering both influenza A and B as an etiologic factor of encephalopathy and other neurological disease in adults.

Immunopathology of Fatal Human Variegated Squirrel Bornavirus 1 Encephalitis, Germany, 2011-2013.

Variegated squirrel bornavirus 1 (VSBV-1) is a zoonotic virus that causes fatal encephalitis in humans who are infected after contact with exotic squirrels. We analyzed the brain lesions and the immune responses in all 4 known human cases that showed panencephalitis. Inflammatory infiltrates in areas positive for VSBV-1 RNA and antigen consisted of CD4+ and CD8+ T cells, with perivascular B-cell accumulation. Strong microglial response and bizarre astroglial expansion were present. Areas of malacia contained neutrophils and foamy microglia and macrophages. Immunopathologic examination during infection showed cleavage of caspase 3 in brain cells adjacent to CD8+ cells and widespread p53 expression, hallmarks of apoptosis. Cerebrospinal fluid analyses over time demonstrated increasing protein concentrations and cell counts, paralleled by pathologic lactate elevations in all patients. The most severe cerebrospinal fluid and histologic changes occurred in the patient with the highest viral load, shortest duration of disease, and most medical preconditions.

Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

Epidemiological Profile of Acute Viral Encephalitis.

OBJECTIVE: To study the etiology and clinico-epidemiological profile of acute viral encephalitis in children with acute encephalitis syndrome (AES). METHODS: An observational study including 100 patients fulfilling the criteria for AES was conducted in children of age group 1 mo - 16 y. Viral isolation was done on RD cells, HEp-2 cells and Vero cells from the cerebrospinal fluid samples of suspected viral encephalitis (VE) cases. An enzyme immunoassay for IgM antibodies was performed for measles, mumps, Varicella zoster virus (VZV), Herpes simplex virus 1 (HSV1) and Japanese encephalitis virus (JEV). Multiplex polymerase chain reaction (PCR) was done for Cytomegalovirus, Epstein Barr virus (EBV), HSV1 & 2, VZV, Enterovirus, Parecho virus, Human Herpes virus (HHV 6, 7) and Parvovirus B19. A micro neutralization test was performed for Enterovirus 71. RESULTS: Out of enrolled 100 patients, 73 were of probable viral encephalitis. HSV1 (31.50%) was the commonest virus followed by Adenovirus (10.95%), Parvovirus (2.73%), JE virus (1.36%), Enterovirus (1.36%), EBV (1.36%), and mixed infection with HSV & EBV (1.36%). HSV 1 caused significant morbidity in children. The common computed tomography (CT) findings were hypodensities in the fronto- parietal lobe followed by cerebral edema. CONCLUSIONS: The landscape of AES in India has changed in the previous decade, and both outbreak investigations and surveillance studies have increasingly reported non-JEV etiologies; because of these findings there is a need to explore additional strategies to prevent AES beyond vector control and JEV vaccination.

Increased serum vascular endothelial growth factor is associated with acute viral encephalitis in Bangladeshi children.

Encephalitis causes significant global morbidity and mortality. A large number of viruses cause encephalitis, and their geographic and temporal distributions vary. In many encephalitis cases, the virus cannot be detected, even after extensive testing. This is one challenge in management of the encephalitis patient. Since cytokines are pivotal in any form of inflammation and vary according to the nature of the inflammation, we hypothesized cytokine levels would allow us to discriminate between encephalitis caused by viruses and other aetiologies. This pilot study was conducted in a tertiary care hospital in Dhaka, Bangladesh. Viral detection was performed by polymerase chain reaction using patient cerebrospinal fluid. Acute phase reactants and cytokines were detected in patient serum. Of the 29 biomarkers assessed using the Wilcoxon rank-sum test, only vascular endothelial growth factor (VEGF) was significantly higher (P = 0.0015) in viral-positive compared with virus-negative encephalitis patients. The area under the curve (AUC) for VEGF was 0.82 (95% confidence interval: 0.66-0.98). Serum VEGF may discriminate between virus-positive and virus-negative encephalitis. Further study will be needed to confirm these findings.

Neurological manifestations of dengue in Central Brazil

Abstract INTRODUCTION: The incidence of dengue has increased throughout the 2000s with a consequent global increase in atypical clinical forms. METHODS: This study reports a series of cases of neurological dengue out of 498 confirmed cases of laboratory dengue in Goiânia, Brazil. Cases were confirmed based on viral RNA detection via polymerase chain reaction or IgM antibody capture. RESULTS: Neurological symptoms occurred in 5.6% of cases, including paresthesia (3.8%), encephalitis (2%), encephalopathy (1%), seizure (0.8%), meningoencephalitis (0.4%), and paresis (0.4%). DENV-3 was the predominant circulating serotype (93%). CONCLUSIONS: We reported dengue cases with neurological manifestations in endemic area.

Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis/myelitis is now a well-known complication after allogeneic stem cell transplantation (allo-HSCT), particularly after cord blood transplantation (CBT). In this study, we evaluated the risk factors of HHV-6 encephalitis/myelitis. METHODS: We evaluated 253 patients who received allo-HSCT from 2007 to 2015 at our institute. HHV-6 encephalitis/myelitis was defined as HHV-6 DNA detection in the cerebrospinal fluid or peripheral blood by polymerase chain reaction in the presence of typical manifestations without other concurrent condition that led to the manifestations. RESULTS: HHV-6 encephalitis/myelitis occurred in 11 patients (4.5%) (9 encephalitis, 3.7%; 2 myelitis, 0.8%). Multivariate analysis showed that CBT, mycophenolate mofetil (MMF) for graft-versus-host disease prophylaxis, history of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and engraftment syndrome (ES) were significantly associated with incidence of HHV-6 encephalitis/myelitis (P=.025, P=.017, P=.017, and P=.014, respectively). CONCLUSION: Although it has been shown that CBT, ES, and history of allo-HSCT are risk factors for HHV-6 encephalitis/myelitis, our study demonstrated MMF is also a risk factor for the disease.

Meningitis en el Hospital Nacional: VI muestra nacional de epidemiología / Meningitis in the National Hospital: VI national epidemiological sample

Introducción: las meningitis constituyen un importante problema de Salud Pública, que afectan de manera especial a los niños menores de 5 años. La etiología más frecuente es viral. Desde la introducción de la vacuna conjugada contra H. influenzae tipo b, S. pneumoniae y N. meningitidis los virus pasaron a ser los agentes más frecuentes. A nivel país, en 2014 y 2015, la etiología viral fue la más frecuente con valores de 69% y 77%, respectivamente, atribuyéndose a las bacterianas como segunda causa. Objetivos: describir las características epidemiológicas de las meningitis, en pacientes de todas las edades internados en el lapso de enero del 2014 a octubre del 2015 en el Hospital Nacional de Itauguá, Paraguay. Metodología: estudio epidemiológico, descriptivo, transversal. Se incluye a pacientes de todas las edades que ingresaron con sospecha de meningitis y/o encefalitis en el periodo de estudio. Resultados: en el periodo de estudio ingresaron 173 casos probables de 201 casos sospechosos de meningitis correspondiendo al 0,5% (173/35140) de todos los ingresos hospitalarios. El grupo etario más afectado fue el de menores de 5 años y entre los mayores de 5 años el de 5 a 14 años. En el 53% procedieron del Departamento Central. Los cuadros clínicos fueron: 98 casos (57%) encefalitis viral, meningitis bacteriana aguda 65 casos (37%), 7 casos (4%) meningitis micótica (Criptococcus). Fallecieron 3 casos de encefalitis y 9 casos de meningitis bacteriana aguda. De 25 casos en edad de vacunarse, 52 % se vacunaron para H. influenzae b y 16% contra P. pneumoniae. No se ha registrado vacunación para N. meningitis en ningún caso. Conclusiones: la incidencia total de meningitis en este periodo de estudio fue de 173 casos. Más de la mitad de los casos fueron de etiología viral. La bacteria más frecuentemente identificada fue S. pneumoniae. En general el grupo de edad más afectado fue el de menores de 5 años. La letalidad fue de 3% en los casos de encefalitis viral, 14% en meningitis bacteriana aguda y 43% en meningitis a Criptococcus. Se desconoce el estado de vacunación de casi la mitad de los casos sobre todo de la antineumocóccica.

Introduction: Meningitis is an important public health problem, which affects children under 5 years of age. The most frequent etiology is viral. Since the introduction of the conjugate vaccine against H. b, S. pneumoniae and N. meningitidis, they became the most frequent agents. In the hole country, in 2014 and 2015, the viral etiology was the most frequent with values ​​of 69% and 77%, respectively, being attributed to the bacterial ones as the second cause. Objectives: To know the epidemiological characteristics of meningitis in all ages hospitalized patients from January 2014 to October 2015 at the National Hospital of Itaugua, Paraguay. Methodology: Epidemiological, descriptive, cross-sectional study. Patients of all ages admitted with suspected meningitis and / or encephalitis were included in the study. Results: During the study, 173 probable cases of 201 suspected cases of meningitis corresponding to 0.5% (173/35140) of all hospital admissions were registered. The more affected age group was the group of children under 5 and among patients with more than 5 years, were between 5 to 14 years; In 53%, they came from the central department.98 cases (57%) were viral encephalitis; Acute bacterial meningitis 65 cases (37%); 7 cases (4%) Fungal Meningitis (Cryptococcus). Of 41 confirmed viral cases (42%), 29 cases (71%) were by Enterovirus. 18 cases of MBA were confirmed; S.pneumoniae (8) or Spn, S were identified. Aureus (4), N.meningitidis (2) or NmStreptococcus group B (1), E. coli (1), S. Epidermidis MR (1) and S. agalactiae (1); From 5 Spn the sero types / serogroups were identified: 6C / 6D (1), serotype14 (1), serotype3 (1), NmW 135 (1), Nmsero group B (1) in a young adult case. There were 3 cases of encephalitis and 9 cases of MBA. Twenty-five cases were vaccinated for Hib and 16% were vaccinated against P.pneumoniae; No vaccination has been registered for Nm. Conclusions: The total incidence of meningitis in this period of study was 173 cases. More than half of the cases were of viral etiology; The most frequently identified bacterium was S. pneumoniae. In general, the most affected age group was children under 5 years of age. The majority coming from the Central department and Cordillera. The lethality was 3% in cases of viral encephalitis; 14% in MBA and 43% in Cryptococcus meningitis. It is unknown the vaccination status of almost half of the cases especially of the anti pneumococcal.

Screening red foxes (Vulpes vulpes) for possible viral causes of encephalitis.

BACKGROUND: Next to various known infectious and non-infectious causes, the aetiology of non-suppurative encephalitis in red foxes (Vulpes vulpes) often remains unclear. Known causes in foxes imply rabies, canine distemper, toxoplasmosis, Aujeszky's disease, as well as parvovirus, adenovirus, circovirus and flavivirus infections. In this study, particular attention was paid on bornaviruses, since red foxes are predators of bicoloured white-toothed shrews, a reservoir of Borna disease virus 1 (BoDV-1). In addition, foxes are known to be highly susceptible for viruses of the order Mononegavirales. METHODS: Analyses for the presence of anti-BoDV-1 antibodies, BoDV-1-RNA and antigen were performed on 225 blood and 59 brain samples, from a total of 232 red foxes. Foxes originated from BoDV-1 endemic and non-endemic German areas. Additional investigations for the presence of rabies, canine distemper, toxoplasmosis, Aujeszky's disease, parvovirus, adenovirus and flavivirus infections were carried out on 16 red foxes with non-suppurative (meningo-) encephalitis. A metagenomic analysis was used on three representative brain samples displaying encephalitis. RESULTS: Among 225 foxes, 37 displayed anti-BoDV-1 antibodies with titres ranging between 1:40 and 1:2560, regardless of geographic origin. In 6 out of 16 foxes with encephalitis, canine distemper virus was detected. No evidence of any of the other investigated agents was found in the 16 fox brains with encephalitis. Metagenomics revealed no infectious agents, except for one already known canine distemper case. CONCLUSION: Red foxes can exhibit BoDV-1 specific antibodies without association with geographic origin or encephalitis due to bornavirus infection. The encephalitis pattern was highly conspicuous for a viral infection, but remained unclear in 10 out of 16 foxes. Thus, presently unknown infectious and non-infectious causes need to be considered and further investigated, especially since foxes also tend to occur in human proximity.

[Cognitive Impairment in Patients with Bacterial Meningitis and Encephalitides].

Cognitive impairments, including dementia, can present as first symptoms at the acute stage, and/or as sequelae in the chronic stages, in some patients with bacterial meningitis (BM) or encephalitides. BM and encephalitides are lifethreatening neurological emergencies, and early recognition, efficient decision-making, and rapid commencement of therapy can be lifesaving. Empirical therapy should be initiated promptly whenever BM or encephalitides are a probable diagnosis. In this article cognitive impairments, including dementia, presenting in patients with BM, Herpes simplex virus encephalitis (HSVE), Human herpesvirus-6 (HHV-6) encephalitis, and Anti N-methyl-d-aspartate (NMDA) receptor encephalitis are reviewed. In the above mentioned diseases, cognitive impairment without fever might be observed at the time of disease onset. cognitive impairment has been also noted in some aged or immunocompromised patients at the onset of BM. Immediate memory disturbance as one of the first symptoms of HHV-6 encephalitis presented in 74% of patients with this disease. Cognitive impairment, including dementia as sequela, was also found in 10-27% of patients with BM, 54-69% of patients with HSVE, 33% of HHV-6 encephalitis patients, and 39% of patients with anti-NMDA receptor encephalitis. Suitable therapeutic management of these diseases at the acute stage is thus required in order to avoid these sequelae.

HHV-6 encephalitis may complicate the early phase after allogeneic hematopoietic stem cell transplantation: Detection by qualitative multiplex PCR and subsequent quantitative real-time PCR.

Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post-HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first-line screening test and real-time PCR for subsequent quantitative evaluation. Five hundred ninety-one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV-6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV-7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV-6 DNA levels demonstrated four of the six HHV-6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV-6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV-6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV-6 encephalitis can be improved by confirming high HHV-6 DNA load in blood.

[Pathogenic Analyses of an Outbreak of Viral Encephalitis Caused by ECHO30 in Guazhou of Gansu Province, China].

We used molecular-biology methods to identify the pathogens that caused an outbreak of viral encephalitis in Guazhou (Gansu province, China)during June-August 2015.We also undertook molecular characterizations of these pathogens. A total of 132samples(14cerebrospinal fluid(CSF)samples;25throat swabs;66serum samples;27fecal samples)were collected from 74 patients during the outbreak of viral encephalitis. For CSF and serum samples, enzyme-linked immunosorbent assay immunoglobulin-M tests were undertaken to detect Japanese encephalitis viruses, enteroviruses, herpes simplex viruses, mumps viruses, and adenoviruses. Real-time polymerase chain reaction was done to detect enteroviruses(including coxsackievirus A16 and enterovirus 71) and the RNA of human adenoviruses. Then, viral isolation was carried out using HEp-2 and RD cells, and the entire VP1 region of positive viral isolates was amplified and sequenced. Finally, molecular characterizations of these pathogens were completed. Seventy two samples were identified as enteroviruses from 132 samples. Among them,71 were identified as echovirus(ECHO)30using enterovirus molecular typing. Japanese encephalitis viruses,herpes simplex viruses, mumps viruses, and adenoviruses were not detected.ECHO30 was isolated from 46 samples out of 29 patients.Similarities in nucleic acids among these ECHO30 isolates were 99.2%-100.0%.ECHO30 from Gansu province and other ECHO30 strains isolated in China since 2011 belonged to a same evolutionary branch.ECHO30 was the pathogen that caused the outbreak of viral encephalitis in Guazhou in 2015.ECHO30 from and Gansu province and ECHO30 isolated in China since 2011 belonged to the same evolutionary branch.

Epidemiology and genetic characterization of BVDV, BHV-1, BHV-4, BHV-5 and Brucella spp. infections in cattle in Turkey.

The aim of the study was to determine the epidemiological data of bovine viral diarrhea virus (BVDV), bovine herpesvirus-1 (BHV-1), bovine herpesvirus-4 (BHV-4), bovine herpesvirus-5 (BHV-5) and Brucella-associated cattle that were previously reported to have abortion and infertility problems in Ankara, Corum, Kirikkale and Yozgat provinces, Turkey. Whole blood and sera samples were obtained from 656 cattle, and antibodies against Brucella spp. were detected in 45 (6.86%) and 41 (6.25%) animals by Rose Bengal plate and serum tube agglutination tests, respectively. The seropositivity rates against BVDV, BHV-1 and BHV-4 were 70.89%, 41.3% and 28.78%, respectively. RT-PCR and PCR were performed to detect RNA and DNA viruses in blood samples, respectively. The BVDV 5'-untranslated region and BHV-1 gB gene detected in this study were phylogenetically analyzed. The BVDV strains analyzed in this study were closely related to those previously reported from Turkey. The nucleotide sequence from the BHV-1 strain detected in this study is the first nucleotide sequence of BHV-1 circulating in this area of Turkey deposited in the GenBank. The presence of Brucella spp. and prevalence of BHV-1, BHV-4 and BVDV in cattle should be further investigated throughout these regions.