Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023.

We report nine severe neonatal infections caused by a new variant of echovirus 11. All were male, eight were twins. At illness onset, they were 3-5 days-old and had severe sepsis and liver failure. This new variant, detected in France since April 2022, is still circulating and has caused more fatal neonatal enterovirus infections in 2022 and 2023 (8/496; 1.6%, seven associated with echovirus 11) compared with 2016 to 2021 (7/1,774; 0.4%). National and international alerts are warranted.

Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023.

Echovirus 11 (E11) has recently been associated with a series of nine neonatal cases of severe hepatitis in France. Here, we present severe hepatitis caused by E11 in a pair of twins. In one of the neonates, the clinical picture evolved to fulminant hepatitis. The E11 genome showed 99% nucleotide identity with E11 strains reported in the cases in France. Rapid genome characterisation using next generation sequencing is essential to identify new and more pathogenetic variants.

Direct next-generation sequencing diagnosis of echovirus 9 meningitis, France.

The prognosis of central nervous system infections caused by enteroviruses partially depends on the viral genotype, which is not provided by current point-of-care diagnostic methods. In this study, next-generation sequencing identified an echovirus 9 directly from the cerebrospinal fluid of a patient presenting with meningitis.

Echovirus type 6 transmission clusters and the role of environmental surveillance in early warning, the Netherlands, 2007 to 2016.

BackgroundIn the Netherlands, echovirus type 6 (E6) is identified through clinical and environmental enterovirus surveillance (CEVS and EEVS). AimWe aimed to identify E6 transmission clusters and to assess the role of EEVS in surveillance and early warning of E6. MethodsWe included all E6 strains from CEVS and EEVS from 2007 through 2016. CEVS samples were from patients with enterovirus illness. EEVS samples came from sewage water at pre-specified sampling points. E6 strains were defined by partial VP1 sequence, month and 4-digit postcode. Phylogenetic E6 clusters were detected using pairwise genetic distances. We identified transmission clusters using a combined pairwise distance in time, place and phylogeny dimensions. ResultsE6 was identified in 157 of 3,506 CEVS clinical episodes and 92 of 1,067 EEVS samples. Increased E6 circulation was observed in 2009 and from 2014 onwards. Eight phylogenetic clusters were identified; five included both CEVS and EEVS strains. Among these, identification in EEVS did not consistently precede CEVS. One phylogenetic cluster was dominant until 2014, but genetic diversity increased thereafter. Of 14 identified transmission clusters, six included both EEVS and CEVS; in two of them, EEVS identification preceded CEVS identification. Transmission clusters were consistent with phylogenetic clusters, and with previous outbreak reports. ConclusionAlgorithms using combined time-place-phylogeny data allowed identification of clusters not detected by any of these variables alone. EEVS identified strains circulating in the population, but EEVS samples did not systematically precede clinical case surveillance, limiting EEVS usefulness for early warning in a context where E6 is endemic.

Upsurge in echovirus 30 detections in five EU/EEA countries, April to September, 2018.

An upsurge in Echovirus 30 (E30) infections, associated with meningitis/meningoencephalitis, has been observed in Denmark, Germany, the Netherlands, Norway and Sweden in the period April to September 2018, compared with 2015-2017. In total, 658 E30 infections among 4,537 enterovirus infections were detected in 15 countries between January and September 2018 and affected mainly newborns and 26-45 year-olds. National public health institutes are reminded to remain vigilant and inform clinicians of the ongoing epidemic.

Seroepidemiology of echovirus 30 in Korean children.

BACKGROUND: Although aseptic meningitis associated with echovirus type 30 has emerged as a global public health concern, no data have been reported on Children's immune status against echovirus type 30. The current study aimed to investigate the seropositivity among Korean children for antibodies against echovirus 30. METHODS: Two hundred and fifty residual serum samples were collected at St. Paul's Hospital. Individuals were categorized by age into four groups: group 1 (3 months-2 years), group 2 (3-6 years), group 3 (7-10 years) and group 4 (11-15 years). Neutralizing antibodies against echovirus 30 were measured. RESULTS: Seroprotective neutralizing antibodies against echovirus 30 were detected in 129 (49%) individuals. Seropositivity rates were 23%, 48%, 55% and 73% in groups 1-4, respectively. For antibody titers, 1:256-1:512 was the highest neutralizing antibody titer range in group 2, while 1:1024-1:2048 in group 3 and 4. Among the seropositive individuals in group 3 and 4, 6% and 12% had neutralizing antibody titers of 1:2048, respectively. CONCLUSIONS: The seropositivity rate increased significantly with age. The distribution of neutralizing antibody titers varied by age group, and higher ranges of neutralizing antibody titers were observed in higher age groups. These findings suggest high susceptibility to echovirus 30 infection in children younger than 2 years old. Echovirus 30 infection in childhood may have contributed to increased neutralizing antibody titers with age.

Viral exanthems: An update on laboratory testing of the adult patient.

Although classic viral exanthems of childhood are well described, they are rarely differentiated in adults. Laboratory techniques for viral identification have advanced without substantial literature to suggest how a dermatologist ought to conduct a cost-effective and diagnostic viral panel. Certain clinical features such as petechiae, vesicles, and dusky macular or morbilliform exanthems point strongly toward a viral exanthem. Differentiation of drug and viral causes of morbilliform eruptions has proven difficult. It is possible that with further diagnostic refinement that unnecessary and fruitless workups of an exanthem and unneeded discontinuation of drugs can be avoided. We review viral exanthems based on clinical features and discuss the available and optimal laboratory techniques to assist the dermatologist in a targeted workup.

Increase in ECHOvirus 6 infections associated with neurological symptoms in the Netherlands, June to August 2016.

The Dutch virus-typing network VIRO-TypeNed reported an increase in ECHOvirus 6 (E-6) infections with neurological symptoms in the Netherlands between June and August 2016. Of the 31 cases detected from January through August 2016, 15 presented with neurological symptoms. Ten of 15 neurological cases were detected in the same province and the identified viruses were genetically related. This report is to alert medical and public health professionals of the circulation of E-6 associated with neurological symptoms.

Laboratory diagnosis and genetic analysis of a family clustering outbreak of aseptic meningitis due to echovirus 30.

Echovirus 30 (E30) is a major pathogen associated with aseptic meningitis. In the summer of 2014, a family clustering aseptic meningitis outbreak occurred in urban-rural fringe of Ningbo city in Zhejiang Province in China. To identify the etiologic agent, specimens were tested by cell culture and reverse transcriptase-polymerase chain reaction. Pathogenic examination confirmed that the outbreak is caused by E30. The first case is a 6-year-old child, who studied in kindergarten in local, suffered from headache and fever. Same symptoms appeared in his parents, aunts, and other six relatives continuously. Meanwhile, vomiting occurred in majority of the patients and diarrhea in parts of them. White blood cells in cerebrospinal fluid (CSF) exceeded normal range in all patients. Protein levels in CSF were above normal range in half of the patients. Glucose levels in CSF were within normal range in all patients. We isolated six strains E30 in the stool specimens of patients, and carried out sequencing analysis to VP1 region. Sequencing results showed that 100% sequence identity was seen in both nucleotide and amino acid levels. Phylogenetic analysis discovered that isolate in this study was grouped into sublineage D2 together with sequences isolated from other areas of China in the 2000s and 2010s. Our study is the first family clustering outbreak of aseptic meningitis caused by E30 in Zhejiang Province in China. It is essential to establish an enterovirus molecular surveillance system in China to prevent mass outbreaks in Zhejiang.

Echovirus 30 meningitis epidemic followed by an outbreak-specific RT-qPCR.

BACKGROUND: An outbreak of enteroviral aseptic meningitis emerged in Southwestern Finland in August 2009. The same enterovirus reappeared with increasing incidence of meningitis in other parts of Finland in 2010. OBJECTIVES: To identify the incidence and molecular epidemiology of enteroviral meningitis outbreak. STUDY DESIGN: The causative agent was identified as echovirus 30 (E-30) by sequencing partial viral protein 1 capsid genome, and a virus type-specific RT-qPCR was set up for sensitive detection of the virus in cerebrospinal fluid specimens. Enterovirus positive CSF specimens were subjected to the E-30-specific assay to investigate this unusual occurrence of aseptic meningitis and facilitate case confirmation during the outbreaks between August 2009 and September 2010. RESULTS: E-30 was detected in 106 (72%) enterovirus positive cerebrospinal fluid specimens. All the meningitis cases in 2009 and most of them in 2010 were among adolescents and several were members of sport teams. CONCLUSIONS: Between August 2009 and September 2010, E-30 caused an extensive outbreak with two peaks in Finland. Type-specific RT-PCR allowed rapid diagnostic follow-up of the epidemic.

Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.

The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross-reacted with non-enteroviruses within the family Picornaviridae. However, all cross-reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non-structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally-infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in-house anti-enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different enterovirus serotypes, including coxsackieviruses A and B, echoviruses, enterovirus A71 and poliovirus.

Serological misdiagnosis of acute liver failure associated with echovirus 25 due to immunological similarities to hepatitis A virus and prozone effect.

We describe a case of acute liver failure caused by echovirus 25 (E25) in a previously healthy 2-year-old boy. Initial serological studies were consistent with hepatitis A virus (HAV), with prozone phenomenon. The similarity of E25 to HAV may obscure accurate diagnosis in some cases of hepatitis.

Persistent spiking fever in a child with acute myeloid leukemia and disseminated infection with enterovirus.

We here report a 7 year old acute myeloid leukemia patient with persistent spiking fever likely caused by chronic echovirus 20 infection. After immunoglobulin substitution fevers subsided and the virus was cleared. Enterovirus infection should be considered in immunocompromised patients with unexplained persistent fever.

Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013.

Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples.

Pleurodynia caused by an echovirus 1 brought back from the tropics.

A 31 year-old woman presented with acute pain on the left side of the thorax and abdomen, radiating to the back together with fever, after she had returned from traveling in Southeast Asia. Except for pleural friction rub auscultated on the left hemithorax, no physical abnormalities were detected. We diagnosed a classical course of Bornholm disease, caused by an echovirus type 1. While described as a classical pathogen causing Bornholm disease, this genotype has not been reported frequently in Surveillance data in the Western World.

Severe hepatitis associated with an echovirus 18 infection in an immune-compromised adult.

Enteroviruses are recognized as important pathogens in pediatric patients; however, they are often overlooked as etiologic agents of disease in adults. Here, we report a case of echovirus 18-associated severe systemic infection and acute liver failure in an adult hematopoietic stem cell transplant recipient. Additionally, we illustrate the utility of molecular methods for the detection and typing of enteroviral infections.