#Kynurenine is a #CSF #biomarker for #bacterial and #viral #CNS #infections (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Kynurenine is a cerebrospinal fluid biomarker for bacterial and viral CNS infections

Kurt-Wolfram Sühs, Natalia Novoselova, Maike Kuhn, Lena Seegers, Volkhard Kaever, Kirsten Müller-Vahl, Corinna Trebst, Thomas Skripuletz, Martin Stangel, Frank Pessler

The Journal of Infectious Diseases, jiz048, https://doi.org/10.1093/infdis/jiz048

Published:  05 February 2019

 

Abstract

Background

The tryptophan-kynurenine-NAD+ pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in CNS infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers.

Methods

We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 220 cerebrospinal fluid samples from patients with bacterial and viral (herpes simplex, varicella zoster, enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (anti-NMDA-R encephalitis, multiple sclerosis), and noninflamed controls (Bell’s palsy, normal pressure hydrocephalus, Tourette syndrome).

Results

Kyn concentrations correlated strongly with CSF markers of neuroinflammation (leukocyte count, lactate, and blood-CSF-barrier dysfunction) and were highly increased in bacterial and viral CNS infections, but were low or undetectable in anti-NMDA-R encephalitis, multiple sclerosis, and controls. Trp was decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed combinations of Kyn, Trp and Kyn/Trp ratio with leukocyte count or lactate as accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation.

Conclusions

The Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation.

Biomarkers, Borrelia, central nervous system, diagnosis, infection, kynurenine, metabolites, tryptophan

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Infectious diseases; Encephalitis; Meningitis.

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CCR2 plays a protective role in #Rocio virus induced #encephalitis by promoting #macrophage infiltration into the #brain (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

CCR2 plays a protective role in Rocio virus induced encephalitis by promoting macrophage infiltration into the brain

Alberto A Amarilla, Nilton Nascimento Santos-Junior, Mario Luis Figueiredo, Joao Paulo Mesquita, Luiz Marcilio, Jorge Fumagalli, David F Colón, Veronica Lippi, Helda Liz Alfonso, Djalma S Lima-Junior, Amanda C Trabuco, Richard L Spinieli, Amanda C Desidera, Christie R A Leite-Panissi, Flávio Lauretti, Silvia Elena Sánchez Mendoza, Cleide Lúcia Araújo, Silva Eduardo Magalhaes Rego, Leonardo J Galvao-Lima, Gabriel S Bassi, Sandra L B Penharvel Martíns, Wilson Gomez Manrique, José Carlos Alves-Filho, Fernando Q Cunha Nias, Y G Peng, Naphak Modhiran, Yin Xiang Setoh, Alexander A Khromykh, Luiz T M Figueiredo, Victor H Aquino Quintana

The Journal of Infectious Diseases, jiz029, https://doi.org/10.1093/infdis/jiz029

Published: 04 February 2019

 

Abstract

Rocio virus (ROCV) is a highly neuropathogenic mosquito-transmitted flavivirus responsible for an unprecedented outbreak of human encephalitis during 1975-1976 in Sao Paulo State, Brazil. Previous studies have shown an increased number of inflammatory macrophages into the central nervous system (CNS) of ROCV-infected mice, implying a role for macrophages in the pathogenesis of ROCV. Here, we showed that ROCV infection results in increased expression of C-C chemokine ligand 2 (CCL2) in the blood and in infiltration of macrophages into the brain. Moreover, we showed using C-C chemokine receptor 2 (CCR2) knockout mice that CCR2 expression was essential for macrophage infiltration in the brains during ROCV infection and that the lack of CCR2 resulted in increased disease severity and mortality. Thus, our findings show the protective role of CCR2-mediated infiltration of macrophages in the brain during ROCV infection.

ROCV, encephalitis, CCL2, macrophages, pathogenesis

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Flavivirus; Rocio Virus; Encephalitis; Animal models.

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#Lyme #Neuroborreliosis is a But Severe and Frequent Neurological Disease in #Mexico (Arch Med Res., abstract)

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

Arch Med Res. 2018 Dec 13. pii: S0188-4409(18)30350-3. doi: 10.1016/j.arcmed.2018.11.007. [Epub ahead of print]

Lyme Neuroborreliosis is a But Severe and Frequent Neurological Disease in Mexico.

Gordillo-Pérez G1, Solorzano F2, Cervantes-Castillo A3, Sanchez-Vaca G4, García-Ramirez R4, Díaz AM5, Muñoz O2, Torres J3.

Author information: 1 Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Unidad Médica de Alta Especialidad Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. Electronic address: lugope2@yahoo.com.mx. 2 Unidad de Investigación, Hospital Infantil de México, Federico Gómez. Secretaria de Salud, Ciudad de México, México. 3 Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Unidad Médica de Alta Especialidad Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. 4 Servicio de Neurología, Unidad Médica de Alta Especialidad Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. 5 Unidad de Medicina Física y Rehabilitación Centro, Unidad Médica de Alta Especialidad Lomas Verdes, Instituto Mexicano del Seguro Social, Ciudad de México, México.

 

Abstract

OBJECTIVE:

To describe clinical cases with neurological manifestations associated with Borrelia burgdorferi infection in a large cohort of children and adults from Mexico.

MATERIAL AND METHODS:

Patients with neurological manifestation (cranial neuritis, radiculoneuritis, meningitis and encephalomyelitis) were recruited in one pediatric and two general hospitals, during January 2006-December 2015. Blood and cerebrospinal fluid (CSF) samples were drawn from each patient at inclusion. IgM and IgG antibodies against B. burgdorferi were detected using a commercial ELISA test, and confirmed by Western-Blot test (WB) using three different antigens from Borrelia burgdorferi complex. Following CDC criteria were considered true cases with both positive tests.

RESULTS:

Of 606 patients recruited, 403 (66.5%) were adults and 203 (33.4%) children, 50.5% were male. B. burgdorferi infection was diagnosed in 168 patients (27.7%), 97 adults, mean age 42 ± 14.7 years and 71 children, mean age 9.6 ± 5 years; early disseminated disease occurred in 130 cases (77.4 %) and chronic stage in 38 (22.6 %). A previous tick bite was reported by 21% cases, and 5% recalled an erythema migrans lesion. Polyradiculoneuropathy and encephalomyelitis were the most common manifestations, whereas 14.8% presented an initial Guillain-Barré Syndrome. B. burgdorferi sensu stricto was identified in 142 (84%) cases, B. garinii in 14 (8%), B. afzelii in three, and nine cases presented coinfection with two species.

CONCLUSION:

Lyme neuroborreliosis is a frequent condition in patients with neurological diseases in Mexico.

Copyright © 2018. Published by Elsevier Inc.

KEYWORDS: Borrelia afzelii; Borrelia garinii; Facial palsy; Guillain-Barré syndrome-like; Lyme neuroborreliosis

PMID: 30554857 DOI: 10.1016/j.arcmed.2018.11.007

Keywords: Lyme Disease; Borrelia burgorferi; GBS; Lyme neuroborreliosis; Encephalitis; Meningitis; Mexico.

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#Enterovirus A71 #Infection and #Neurologic Disease, Madrid, #Spain, 2016 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 1—January 2019 / CME ACTIVITY – Synopsis

Enterovirus A71 Infection and Neurologic Disease, Madrid, Spain, 2016

Carmen Niño Taravilla1  , Isabel Pérez-Sebastián1, Alberto García Salido, Claudia Varela Serrano, Verónica Cantarín Extremera, Anna Duat Rodríguez, Laura López Marín, Mercedes Alonso Sanz, Olga María Suárez Traba, and Ana Serrano González

Author affiliations: Hospital Infantil Universitario Niño Jesús, Madrid, Spain

 

Abstract

We conducted an observational study from January 2016 through January 2017 of patients admitted to a reference pediatric hospital in Madrid, Spain, for neurologic symptoms and enterovirus infection. Among the 30 patients, the most common signs and symptoms were fever, lethargy, myoclonic jerks, and ataxia. Real-time PCR detected enterovirus in the cerebrospinal fluid of 8 patients, nasopharyngeal aspirate in 17, and anal swab samples of 5. The enterovirus was genotyped for 25 of 30 patients; enterovirus A71 was the most common serotype (21/25) and the only serotype detected in patients with brainstem encephalitis or encephalomyelitis. Treatment was intravenous immunoglobulins for 21 patients and corticosteroids for 17. Admission to the pediatric intensive care unit was required for 14 patients. All patients survived. At admission, among patients with the most severe disease, leukocytes were elevated. For children with brainstem encephalitis or encephalomyelitis, clinicians should look for enterovirus and not limit testing to cerebrospinal fluid.

Keywords: EV-A71; Encephalitis; Spain.

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#Surveillance of #enteroviruses from #paediatric patients attended at a tertiary #hospital in #Catalonia from 2014 to 2017 (J Clin Virol., abstract)

[Source: Science Direct, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 30 November 2018 / In Press, Accepted Manuscript

Surveillance of enteroviruses from paediatric patients attended at a tertiary hospital in Catalonia from 2014 to 2017

Cristina Andrés a, Jorgina Vila b, Laura Gimferrer a , Maria Piñana a, Juliana Esperalba a, Maria Gema Codina a, Meritxell Barnés b, Mariadel Carmen Martín a, Francisco Fuentes a, Susana Rubio a, Pilar Alcubilla a, Carlos Rodrigo b, Tomàs Pumarola a, Andrés Antón a

{a} Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; {b} Paediatric Hospitalisation Unit, Department of Paediatrics, Hospital Universitari Maternoinfantil Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

Received 4 September 2018, Revised 26 October 2018, Accepted 16 November 2018, Available online 30 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.004

 

Highlights

  • The study reports virological and clinical enterovirus surveillance in Catalonia.
  • The four enterovirus species cocirculated, distinguishing up to 27 different types.
  • Most of neurological studied cases were from the 2016 spring outbreak.
  • EV-A71 was one of the most detected EV, mostly during the outbreak.
  • Rhombencephalitis cases were related to EV-A71 infection.
  • EV-D68 was associated with lower respiratory tract infections.
  • Necessity to perform EV surveillance in primary care settings.

 

Abstract

Background

Enterovirus (EV) infections are usually asymptomatic or mild, but symptomatic infections can evolve to severe complications. Outbreaks of EV-A71 and EV-D68 have been recently reported worldwide, sometimes related to severe clinical outcomes.

Objective

To describe EV genetic diversity and the clinical outcomes from paediatric patients attended at a tertiary university hospital in Barcelona (Catalonia, Spain) from 2014 to 2017.

Study design

Specimens were collected from paediatric (<17 years old) cases with suspicion of respiratory tract infection or EV infection. EV laboratory-confirmation was performed by specific real-time multiplex RT-PCR assay. Partial viral VP1 protein was sequenced for genetic characterisation by phylogenetic analyses.

Results

A total of 376 (7%) from 5,703 cases were EV laboratory-confirmed. Phylogenetic analyses of VP1 (210; 81%) sequences distinguished up to 27 different EV types distributed within EV-A (82; 40%), EV-B (90; 42%), EV-C (5; 2%), and EV-D (33; 15%), in addition to 50 (19%) rhinoviruses. The most predominant were EV-A71 (37; 45%) and EV-D68 (32; 99%). EV-A71 was highly related to neurological complications (25/39, 63%), of which 20/39 were rhombencephalitis, and most EV-D68 (28/32, 88%) were associated with lower respiratory tract infections (LRTI), and exceptionally one (3%) with flaccid paralysis.

Conclusions

EV-A71 and EV-D68 were the most detected EV in respiratory specimens. EV-A71 was highly related to neurological disease and EV-D68 was often associated with LRTI. However, both potential relatedness to neurological diseases makes the monitoring of EV circulation obligatory.

Keywords: enteroviruses – respiratory infections – surveillance – genetic diversity – molecular epidemiology – paediatric population

© 2018 Elsevier B.V. All rights reserved.

Keywords: Enterovirus; EV-A71; EV-D68; Rhomboencephalitis; AFP; Spain.

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#Varicella-zoster Virus #Clades Circulating in #Spain over two decades (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 28 November 2018 / In Press, Accepted Manuscript

Varicella-zoster Virus Clades Circulating in Spain over two decades

Irene González 1, Alejandro Molina 1, Pilar Pérez-Romero, Juan Emilio Echevarría, Lante He, David Tarragó

Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Spain

Received 5 June 2018, Revised 30 August 2018, Accepted 26 November 2018, Available online 28 November 2018.

DOI: https://doi.org/10.1016/j.jcv.2018.11.008

 

Highlights

  • In this first Spanish molecular epidemiological study, encephalitis was more frequent in patients infected with VZV clades within genogroup E, suggesting earlier introduction of these clades.
  • First evidence of recombination in Spain: VZV clade 1 and clade 3 recombinants were found in six cases.
  • VZV clade 2 vaccine strains were found in three patients with herpes zoster and one with neurological disease (encephalitis and retinitis).

 

Abstract

Background

Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain.

Objectives

To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016.

Study Design

In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs.

Results

Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001).

Conclusions

Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.

Abbreviations: VZV: Varicella-zoster virus – CSF: Cerebral Spinal Fluid – ORF: Open reading frame – vOKA: vaccine-OKA – bp: base pair – y.o.: years old – SNPs: Single Nucleotide Polymorphisms

Keywords: Varicella zoster virus – Recombination – Clade – Genotype – Vaccine – Molecular epidemiology

{1} These authors contributed equally to this study.

© 2018 Elsevier B.V. All rights reserved.

Keywords: Varicella; Encephalitis; Spain; VZV.

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Potential role of #dengue virus, #chikungunya virus and #Zika virus in #neurological diseases (Mem Inst Oswaldo Cruz, abstract)

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

Mem Inst Oswaldo Cruz. 2018 Oct 29;113(11):e170538. doi: 10.1590/0074-02760170538.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases.

Vieira MADCES1,2,3, Costa CHN4, Linhares ADC5, Borba AS2, Henriques DF6, Silva EVPD6, Tavares FN5, Batista FMA7, Guimarães HCL7, Martins LC6, Monteiro TAF3,5, Cruz ACR6, Azevedo RDSDS6, Vasconcelos PFDC6.

Author information: 1 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Neurologia, Teresina, PI, Brasil. 2 Fundação Municipal de Saúde de Teresina, Diretoria de Vigilância em Saúde, Teresina, PI, Brasil. 3 Instituto Evandro Chagas, Programa de Pós-Graduação em Virologia, Ananindeua, PA, Brasil. 4 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Infectologia, Teresina, PI, Brasil. 5 Instituto Evandro Chagas, Seção de Virologia Geral, Ananindeua, PA, Brasil. 6 Instituto Evandro Chagas, Seção de Arbovirologia e Febres Hemorrágicas, Ananindeua, PA, Brasil. 7 Secretaria de Estado da Saúde do Piauí, Diretoria da Unidade de Vigilância e Assistência à Saúde, Teresina, PI, Brasil.

 

Abstract

This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

PMID: 30379197 DOI: 10.1590/0074-02760170538

Keywords: Arbovirus; Chikungunya Fever; Dengue Fever; Zika Virus; Encephalitis; GBS; Encephalomyelitis.

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