#Zoonotic #spillover #infections with #Borna disease virus 1 leading to #fatal #human #encephalitis, 1999–2019: an epidemiological investigation (J Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation

Hans Helmut Niller, MD †, Klemens Angstwurm, MD †, Dennis Rubbenstroth, DVM †, Kore Schlottau, PhD, Arnt Ebinger, MSc, Sebastian Giese, PhD, Silke Wunderlich, MD, Prof Bernhard Banas, MD, Leonie F Forth, PhD, Donata Hoffmann, DVM, Dirk Höper, PhD, Prof Martin Schwemmle, PhD, Prof Dennis Tappe, MD, Prof Jonas Schmidt-Chanasit, MD, Daniel Nobach, DVM, Prof Christiane Herden, DVM, Prof Christoph Brochhausen, MD, Natalia Velez-Char, MD, Andreas Mamilos, MD, Kirsten Utpatel, MD, Prof Matthias Evert, MD, Saida Zoubaa, MD, Prof Markus J Riemenschneider, MD, Viktoria Ruf, MD, Prof Jochen Herms, MD, Georg Rieder, MD, Mario Errath, MD, Prof Kaspar Matiasek, DVM, Prof Jürgen Schlegel, MD, Friederike Liesche-Starnecker, MD, Bernhard Neumann, MD, Kornelius Fuchs, MD, Prof Ralf A Linker, MD, Prof Bernd Salzberger, MD, Tobias Freilinger, MD, Lisa Gartner, MD, Prof Jürgen J Wenzel, MD, Prof Udo Reischl, PhD, Prof Wolfgang Jilg, MD, Prof André Gessner, MD, Prof Jonathan Jantsch, MD, Prof Martin Beer, DVM  †, Prof Barbara Schmidt, MD †

Published: January 07, 2020 / DOI: https://doi.org/10.1016/S1473-3099(19)30546-8




In 2018–19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis.


All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999–2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed.


BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir.


BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions.


German Federal Ministry of Education and Research.

Keywords: Borna Disease Virus 1; Encephalitis; Human; Germany.


An #update on #Toscana virus #distribution, #genetics, medical and diagnostic aspects (Clin Microbiol Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Microbiol Infect. 2020 Jan 2. pii: S1198-743X(19)30672-X. doi: 10.1016/j.cmi.2019.12.015. [Epub ahead of print]

An update on Toscana virus distribution, genetics, medical and diagnostic aspects.

Ayhan N1, Charrel RN2.

Author information: 1 Unite des Virus Emergents (Aix-Marseille Univ – IRD 190 – Inserm 1207 – IHU Mediterranee Infection), Marseille, France; EA7310, Laboratoire de Virologie, Université de Corse-Inserm, Corte, France. 2 Unite des Virus Emergents (Aix-Marseille Univ – IRD 190 – Inserm 1207 – IHU Mediterranee Infection), Marseille, France. Electronic address: remi.charrel@univ-amu.fr.




Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data as demonstrated by less than 250 peer-reviewed articles since the 1970’s.


The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles in order to provide an updated review highlighting recent findings to complement previous review articles.


PubMed database was searched using the “Toscana virus” keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles.


Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Beside the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis that have been reported for forty years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness, facial paralysis.


Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations.

Copyright © 2019. Published by Elsevier Ltd.

PMID: 31904562 DOI: 10.1016/j.cmi.2019.12.015

Keywords: Arbovirus; Toscana virus; Encephalitis; Meningitis; Neurology.


#Human #Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic #Pathogens of the #CNS? (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Dec 20;12(1). pii: E14. doi: 10.3390/v12010014.

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Desforges M1, Le Coupanec A1, Dubeau P1, Bourgouin A1, Lajoie L2, Dubé M1,3, Talbot PJ1.

Author information: 1 Laboratory of Neuroimmunovirology, Institut national de la recherche scientifique (INRS)-Institut Armand-Frappier, Université du Québec, Laval, QC H7V 1B7, Canada. 2 Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada. 3 Research Centre of the Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H3T 1J4, Canada.



Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

KEYWORDS: CNS infection; acute and chronic neurological diseases; encephalitis; encephalopathy; human coronavirus; human respiratory virus; neuroinvasion; respiratory viral infection

PMID: 31861926 DOI: 10.3390/v12010014

Keywords: Coronavirus; Neuroinvasion; Encephalopathy; Neurology.


#Encephalitis caused by type B #influenza virus in an adult. Report of one case (Rev Med Chil., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Med Chil. 2019 Jul;147(7):922-927. doi: 10.4067/S0034-98872019000700922.

[Encephalitis caused by type B influenza virus in an adult. Report of one case].

[Article in Spanish]

Reyes C1, Miranda S, Fica A2, Navarrete M3.

Author information: 1 Sub Departamento de Neurología, Hospital Base de Valdivia, Valdivia, Chile. 2 Subdepartamento de Medicina, Hospital Base de Valdivia, Valdivia, Chile. 3 Laboratorio de Biología Molecular, Hospital Base de Valdivia, Valdivia, Chile.



Neurological manifestations associated with influenza virus infection include encephalitis, encephalopathy, acute necrotizing encephalitis, transverse myelitis, acute disseminated encephalomyelitis, mild encephalitis with reversible splenial syndrome (MERS), and Guillaín Barré syndrome. We report a 16-year-old female who was admitted at our emergency department with seizures, confusion, nystagmus and motor clumsiness five days after an upper a respiratory tract infection. Influenza type B virus infection was confirmed by chain polymerase reaction analysis. The initial electroencephalogram demonstrated a pattern of global slowness without epileptic discharges. One week later, it showed a progression to slow-wave focal bilateral discharges at both temporal and occipital lobes. The patient had a favorable evolution and was discharged 19 days after admission with phenytoin to prevent seizures.

PMID:  31859991 DOI: 10.4067/S0034-98872019000700922

Keywords: Seasonal Influenza; Influenza B; Encephalitis; Neurology.


#Clinical characteristics of #EVA71 #neurological disease during an #outbreak in #children in #Colorado, #USA, in 2018: an observational cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study

Kevin Messacar, MD, Emily Spence-Davizon, MPH, Christina Osborne, MD, Craig Press, MD, Teri L Schreiner, MD, Jan Martin, MD, Ricka Messer, MD, John Maloney, MD, Alexis Burakoff, MD, Meghan Barnes, MSPH, Shannon Rogers, MS, Adriana S Lopez, MPH, Janell Routh, MD, Susan I Gerber, MD, M Steven Oberste, PhD, W Allan Nix, BS, Prof Mark J Abzug, MD, Prof Kenneth L Tyler, MD, Rachel Herlihy, MD, Samuel R Dominguez, MD

Published: December 16, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30632-2




In May, 2018, Children’s Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak.


In this retrospective observational cohort study, children (younger than 18 years) who presented to Children’s Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018.


Between March 10 and Nov 10, 2018, 74 children presenting to Children’s Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0–31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1–2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover.


This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance.



Keywords: Enterovirus; EV-A71; Neurology; Pediatrics; AFM; Meningitis; Encephalitis; USA; Colorado.


Characteristics and outcome of #influenza-associated #encephalopathy / #encephalitis among #children in a tertiary pediatric #hospital in #Italy, 2017-2019 (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2019 Nov 29;19(1):1012. doi: 10.1186/s12879-019-4636-5.

Characteristics and outcome of influenza-associated encephalopathy/encephalitis among children in a tertiary pediatric hospital in Italy, 2017-2019.

Mastrolia MV1, Rubino C2, Resti M3, Trapani S3, Galli L4.

Author information: 1 Post-graduate School of Pediatrics, University of Florence, Viale Gaetano Pieraccini, 24, 50139, Florence, Italy. maria.mastrolia@unifi.it. 2 Post-graduate School of Pediatrics, University of Florence, Viale Gaetano Pieraccini, 24, 50139, Florence, Italy. 3 Pediatric Department, Anna Meyer Children’s University Hospital, Florence, Italy. 4 Department of Health Sciences University of Florence, Paediatric Infectious Diseases Division, Anna Meyer Children’s University Hospital, Florence, Italy.




Influenza is the most frequent cause of acute upper respiratory tract infections during winter season. Although rare, neurological manifestations are known to occur during influenza infection and approximatively three-quarters of cases are in children. In this study, we aimed to characterize the burden and clinical spectrum of influenza-associated encephalopathy and encephalitis in children admitted at a tertiary pediatric hospital in Italy over two influenza seasons (2017-2019).


We retrospectively analyzed clinical, laboratory, instrumental data and outcome of patients discharged with ICD9-CM 487.0 code.


Fifteen children (13.1% of those discharged with a diagnosis of influenza infection in the study period), had influenza-associated central nervous system (CNS) manifestations. Eight patients (53.3%) were diagnosed as influenza encephalitis, 7 (46.7%) as influenza encephalopathy. Median age was 27 months. In children under 2 years of age (40% of all cases) altered consciousness was the most frequent neurological manifestation while respiratory symptoms were present at admission in all cases. Younger children also required intensive care support more frequently. Five subjects (33.3%) presented comorbidity. None of the patients had received seasonal influenza vaccination. The median time from onset of respiratory signs to onset of neurological manifestations was 24 h. Cerebrospinal fluid (CSF) analysis was normal in most patients and polymerase chain reaction for influenza virus RNA on CSF, when performed, was negative in all samples. Neuroradiological investigations, performed in 5 children, reported cortical and subcortical white matter signal alterations. Oseltamivir was administered only in 2 cases. Fourteen patients recovered without sequelae, and only a 2-year-old girl had minimal impairment in fine motor skills at discharge.


All children presenting acute neurological features during influenza season should be evaluated for influenza-associated CNS complications even if the respiratory involvement is mild. Absence of underlying diseases or other risk factors are not protective factors against CNS influenza-associated complications. The lack of CSF pleocytosis does not exclude CNS involvement. Children under 2 years of age are at higher risk of requiring intensive care support.

KEYWORDS: Children; Clinical characteristics; Encephalitis; Encephalopathy; Influenza; Outcome

PMID: 31783806 DOI: 10.1186/s12879-019-4636-5

Keywords: Seasonal Influenza; Encephalitis; Encephalopathy; Pediatrics; Italy.


#Jamestown Canyon Virus #Encephalitis in a #Heart #Transplant Patient (Transpl Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transpl Infect Dis. 2019 Nov 12:e13210. doi: 10.1111/tid.13210. [Epub ahead of print]

Jamestown Canyon Virus Encephalitis in a Heart Transplant Patient.

Askar W1, Menaria P2, Thohan V3, Brummitt CF4.

Author information: 1 Department of Internal Medicine Residency, Aurora Healthcare, Milwaukee, WI. 2 Department of Hospital Medicine, Aurora St. Luke’s Medical Center, Aurora Healthcare, Milwaukee, WI. 3 Department of Advanced Heart Failure Therapies, Mission Health System, Asheville, NC. 4 Department of Infectious Diseases, Aurora Healthcare, Milwaukee, WI.



Jamestown Canyon virus (JtCV) is an arbovirus and a member of the California serogroup. To our knowledge, all the cases of JtCV have been reported in immunocompetent patients since it was first detected in 1997. We report a case of JtCV encephalitis in a solid organ transplant patient. A 48-year-old female from Wisconsin had multiple hospital admissions for symptoms of progressive confusion, visual hallucinations, and inability to perform self-care. Initial evaluation was significant for lymphocytes in cerebrospinal fluid (CSF), and multiple infectious and metabolic causes were excluded. Further investigation found JtCV IgM in serum, and CSF. The patient’s clinical course was compatible with JtCV encephalitis and she was treated with ribavirin in addition to reduction of her immunosuppressive medications. She showed gradual and significant improvement in her mental and functional status. JtCV can cause a variety of symptoms that range from a flu-like syndrome to encephalitis. There have been an increased number of reported cases in recent years which is attributed to increased physician awareness and the availability of laboratory testing. Optimal treatment is still not known.

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PMID: 31713971 DOI: 10.1111/tid.13210

Keywords: Jamestown Canyon Virus; Arbovirus; Encephalitis; USA; Wisconsin; Organ transplantation.