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:




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.


Unbiased #Metagenomic #Sequencing for #Pediatric #Meningitis in #Bangladesh Reveals #Neuroinvasive #Chikungunya Virus #Outbreak and Other Unrealized Pathogens (MBio, abstract)

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

Unbiased Metagenomic Sequencing for Pediatric Meningitis in Bangladesh Reveals Neuroinvasive Chikungunya Virus Outbreak and Other Unrealized Pathogens

Senjuti Saha, Akshaya Ramesh, Katrina Kalantar, Roly Malaker, Md Hasanuzzaman, Lillian M. Khan, Madeline Y. Mayday, M. S. I. Sajib, Lucy M. Li, Charles Langelier, Hafizur Rahman, Emily D. Crawford, Cristina M. Tato, Maksuda Islam, Yun-Fang Juan, Charles de Bourcy, Boris Dimitrov, James Wang, Jennifer Tang, Jonathan Sheu, Rebecca Egger, Tiago Rodrigues De Carvalho, Michael R. Wilson, Samir K. Saha, Joseph L. DeRisi

Nisha Duggal, Editor

DOI: 10.1128/mBio.02877-19



The burden of meningitis in low-and-middle-income countries remains significant, but the infectious causes remain largely unknown, impeding institution of evidence-based treatment and prevention decisions. We conducted a validation and application study of unbiased metagenomic next-generation sequencing (mNGS) to elucidate etiologies of meningitis in Bangladesh. This RNA mNGS study was performed on cerebrospinal fluid (CSF) specimens from patients admitted in the largest pediatric hospital, a World Health Organization sentinel site, with known neurologic infections (n = 36), with idiopathic meningitis (n = 25), and with no infection (n = 30), and six environmental samples, collected between 2012 and 2018. We used the IDseq bioinformatics pipeline and machine learning to identify potentially pathogenic microbes, which we then confirmed orthogonally and followed up through phone/home visits. In samples with known etiology and without infections, there was 83% concordance between mNGS and conventional testing. In idiopathic cases, mNGS identified a potential bacterial or viral etiology in 40%. There were three instances of neuroinvasive Chikungunya virus (CHIKV), whose genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause febrile illness in 2017. CHIKV-specific qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 (n = 472) revealed 17 additional CHIKV meningitis cases, exposing an unrecognized meningitis outbreak. Orthogonal molecular confirmation, case-based clinical data, and patient follow-up substantiated the findings. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis, conduct surveillance, and predict outbreaks. The improved patient- and population-level data can inform evidence-based policy decisions.



Globally, there are an estimated 10.6 million cases of meningitis and 288,000 deaths every year, with the vast majority occurring in low- and middle-income countries. In addition, many survivors suffer from long-term neurological sequelae. Most laboratories assay only for common bacterial etiologies using culture and directed PCR, and the majority of meningitis cases lack microbiological diagnoses, impeding institution of evidence-based treatment and prevention strategies. We report here the results of a validation and application study of using unbiased metagenomic sequencing to determine etiologies of idiopathic (of unknown cause) cases. This included CSF from patients with known neurologic infections, with idiopathic meningitis, and without infection admitted in the largest children’s hospital of Bangladesh and environmental samples. Using mNGS and machine learning, we identified and confirmed an etiology (viral or bacterial) in 40% of idiopathic cases. We detected three instances of Chikungunya virus (CHIKV) that were >99% identical to each other and to a strain previously recognized to cause systemic illness only in 2017. CHIKV qPCR of all remaining stored 472 CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital uncovered an unrecognized CHIKV meningitis outbreak. CSF mNGS can complement conventional diagnostic methods to identify etiologies of meningitis, and the improved patient- and population-level data can inform better policy decisions.

Keywords: Chikungunya fever; Meningitis; Pediatrics; Bangladesh; Neuroinvasion.


#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:




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.


#Epidemiology and #complications of late-onset #sepsis: an #Italian area-based study (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]


Epidemiology and complications of late-onset sepsis: an Italian area-based study

Alberto Berardi , Francesca Sforza, Lorenza Baroni, Caterina Spada, Simone Ambretti, Giacomo Biasucci, Serenella Bolognesi, Mariagrazia Capretti, Edoardo Carretto, Matilde Ciccia, Marcello Lanari, Maria Federica Pedna, Vittoria Rizzo,  [ … ], Maria Letizia Bacchi Reggiani


Published: November 22, 2019 / DOI:




Most studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance.


This is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired).


During the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics.


This study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate.


Citation: Berardi A, Sforza F, Baroni L, Spada C, Ambretti S, Biasucci G, et al. (2019) Epidemiology and complications of late-onset sepsis: an Italian area-based study. PLoS ONE 14(11): e0225407.

Editor: Umberto Simeoni, Centre Hospitalier Universitaire Vaudois, FRANCE

Received: May 16, 2019; Accepted: November 3, 2019; Published: November 22, 2019

Copyright: © 2019 Berardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files

Funding: AB Part of the research leading to these results has received funding from the European Community’s Seventh Framework Programme [FP7/2007-2013] under grant agreement n° HEALTH-F7-2007-200481 DEVANI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: This is my amended Competing Interests Statement: Professor Alberto Berardi has received fees (in 2018) from a commercial funder (GSK) for a phone interview. This does not alter adherence to PLOS ONE policies on sharing data and materials. I declare that there are no competing interest concerning the content of this manuscript. I have no further relevant declarations relating to employment, consultancy, patents, products in development, marketed products.

Keywords: Sepsis; Meningitis; Pneumonia; Intensive Care; Pediatrics; Italy.


#Streptococcus suis–Associated #Meningitis, #Bali, #Indonesia, 2014–2017 (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 12—December 2019 / CME ACTIVITY – Research

Streptococcus suis–Associated Meningitis, Bali, Indonesia, 2014–2017

Ni Made Susilawathi, Ni Made Adi Tarini, Ni Nengah Dwi Fatmawati, Putu I.B. Mayura, Anak Agung Ayu Suryapraba, Made Subrata, Anak Agung Raka Sudewi, and Gusti Ngurah Mahardika

Author affiliations: Udayana University, Denpasar, Bali, Indonesia



Streptococcus suis is an emerging agent of zoonotic bacterial meningitis in Asia. We describe the epidemiology of S. suis cases and clinical signs and microbiological findings in persons with meningitis in Bali, Indonesia, using patient data and bacterial cultures of cerebrospinal fluid collected during 2014–2017. We conducted microbiological assays using the fully automatic VITEK 2 COMPACT system. We amplified and sequenced gene fragments of glutamate dehydrogenase and recombination/repair protein and conducted PCR serotyping to confirm some serotypes. Of 71 cases, 44 were confirmed as S. suis; 29 isolates were serotype 2. The average patient age was 48.1 years, and 89% of patients were male. Seventy-seven percent of patients with confirmed cases recovered without complications; 11% recovered with septic shock, 7% with deafness, and 2% with deafness and arthritis. The case-fatality rate was 11%. Awareness of S. suis infection risk must be increased in health promotion activities in Bali.

Keywords: Streptococcus suis; Meningitis; Indonesia.


#Prediction of unfavorable #outcomes in #WNV #neuroinvasive #infection – result of a multinational ID-IRI study (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 11 November 2019, 104213 / In Press, Journal Pre-proof

Prediction of unfavorable outcomes in West Nile virus neuroinvasive infection – result of a multinational ID-IRI study

Corneliu Petru Popescu a,b,c,1, Simin Aysel Florescu a,b,1, Rodrigo Hasbun d, Arjan Harxhi e, Razi Evendar f, Hasip Kahraman g, Ami Neuberger f, Daniel Codreanu b, Mihaela Florentina Zaharia a,b,c, Selma Tosun h, Emanoil Ceausu b, Simona Maria Ruta a,i, Gorana Dragovacj, k, Natalia Pshenichnaya l,m, Galina Gopatsa n, Olga Shmaylenko o, Éva Nagy, p, Jelena Djekic Malbasaj k, Mirjana Strbac j, Nenad  Pandak q, Husnu Pullukcu g, Botond Lakatos p, Yasemin Cag r, Antonio Cascio s, Ilaria Coledan t, Serkan Oncu u, Hakan Erdemc v

{a} University of Medicine and Pharmacy Carol Davila Bucharest, Romania; {b} Dr Victor Babes Clinical Hospital of Infectious and Tropical Diseases Bucharest, Romania; {c} ESCMID Study Group for Infectious Diseases of the Brain – ESGIB, Switzerland; {d} Department of Infectious Diseases, UT Health McGovern Medical School, Houston, TX, USA; {e} Service of Infectious Disease, University Hospital Center of Tirana, Tirana, Albania; {f} Infectious Diseases Institute, Rambam Health Care Campus, Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel; {g}
Ege University, School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Izmir, Turkey; {h} Department of Infectious Diseases and Clinical Microbiology, Izmir Bozyaka Training and Research Hospital, Izmir, Turkey; {i} Stefan S. Nicolau Institute of Virology, Bucharest, Romania; {j} Institute of Public Health of Vojvodina, Department of Prevention and Control of Diseases, Novi Sad, Serbia; {k}
University of Novi Sad, Faculty of Medicine, Department of Epidemiology, Novi Sad, Serbia; {l} National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Moscow, Russia; {m} Central Scientific Research Laboratory, Rostov State Medical University, Rostov-on-Don, Russia; {n} Department of Infectious Diseases, Rostov State Medical University, Rostov-on-Don, Russia; {o} Department of Infectious Diseases #5, City Hospital #1 named after N.A. Semashko, Rostov-on-Don, Russia; {p}
National Institute of Hematology and Infectious Diseases, Saint Laszlo Hospital, Budapest, Hungary; {q} General Hospital Slavonski Brod, Department for Infectious Diseases, School of Medicine, University of Split, Split, Croatia; {r} Department of Infectious Diseases and Clinical Microbiology, Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey; {s} Section of Infectious and Tropical Diseases, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Italy; {t} Department of Diagnostics and Public Health, Section of Infectious Diseases, University of Verona, Verona, Italy; {u} Department of Infectious Diseases and Clinical Microbiology, Adnan Menderes University School of Medicine, Aydin, Turkey; {v} ID-IRI, Ankara, Turkey

Received 30 August 2019, Revised 31 October 2019, Accepted 7 November 2019, Available online 11 November 2019. DOI:



  • Prognosis of unfavorable outcomes in West Nile virus neuroinvasive infection.
  • The relative risk for death by age.
  • Encephalitis, meningoencephalitis, meningitis.
  • Glasgow coma score was correlated with evolution to death.
  • Risk score was calculated according to age, co-morbidities, clinical manifestations.




WNV causes 1.4% of all central nervous system infections and is the most common cause of epidemic neuro-invasive disease in humans.


Our main objective was to investigate retrospectively West Nile virus neuroinvasive disease (WNND) cases hospitalized during 2010- 2017 and identified factors that can influence prognosis.

Study design

We documented the demographic, epidemiologic, clinical and laboratory data of WNND and identified factors that can influence prognosis. The data were recruited through Infectious Diseases International Research Initiative (ID-IRI), which serves as a network for clinical researches.


We investigated 165 patients with WNND in 10 countries from three continents. 27 patients died and the mortality rate was 16.4%. In an univariate analysis age, congestive heart failure, neoplasm and ischemic heart disease (p < 0.001), neuropsychiatric disorders (p = 0.011), chronic hepatitis (p = 0.024) and hypertension (p = 0.043) were risk factors for death. Fatal evolution was also correlated with ICU addmission, disorientation, speech disorders, change in consciousnes, coma, a low Glasgow coma score, obtundation, confusion (p < 0.001), history of syncope (p = 0.002) and history of unconsciousness (p = 0.037). In a binomial logistic regresssion analysis only age and coma remained independent prediction factors for death. We created an equation that was calculated according to age, co-morbidities and clinical manifestations that may be used to establish the prognosis of WNND patients.


WNND remain an important factor for morbidity and mortality worldwide, evolution to death or survival with sequelae are not rare. Our study creates an equation that may be used in the future to establish the prognosis of WNND patients.

Keywords: West Nile virus – WNV – meningitis – encephalitis – neuroinvasive – death

{1} These authors contributed equally to this article.

© 2019 Elsevier B.V. All rights reserved.

Keywords: WNV; WNND; Neuroinvasion; Encephalitis; Meningitis; European Region.


Emergence of #ceftriaxone #resistance during a #pneumococcal #meningitis with #fatal evolution (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence of ceftriaxone resistance during a pneumococcal meningitis with fatal evolution

A. Mizrahi, J.C. Marvaud, B. Pilmis, J.C. Nguyen Van, C. Couzigou, C. Bruel, N. Engrand, A. Le Monnier, T. Lambert

DOI: 10.1128/AAC.01958-19



We report a case of a 62-year old man treated for a Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After a neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in serum and CSF. S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid ten days after the isolation of the first strain. Isolates analysis showed that a mutation of penicillin-binding proteins in PBP2x has occurred under treatment.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Ceftriaxone; Streptococcus pneumoniae; Meningitis.