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Background Human parechovirus (HPeVs), along with human enteroviruses are associated with gastrointestinal and respiratory infections. The aim of this study was to assess the performance characteristics of two nucleic acid extraction for HPeV-RNA quantitation, the RNAlev Extraction Kit associated with Maxwell automated nucleic acid extractor (Promega, Mi, Italy) and RNAzol manually protocol. Methods A total of 137 fecal specimens previously routinely screened for rotavirus and adenovirus were tested for HPeV virus. Results Methods 1 and 2 detected HPeV-RNA in 11 and 10 samples, respectively, with a 96.2% concordance. In particular, 124/137 (90.5%) were concordantly negative by both methods; 8/137 (5.8%) concordantly positive. For the 8 specimens that were positive by both tests, the population mean (SD) was 320 (601) copies/mg with method 1 and 1216 (2338) copies/mg with method 2. By referring to the 8 specimens that were concordantly positive, the correlation value between the two methods was not statistically significant (r = 0.381 and p=0.3599). Bland-Altman analysis showed that differences between the two methods were within ±1000 copies/mg of the averaged results for all of the tested specimens. Conclusions Method 2, being a semi-automated method, provides benefits over a manual method, in terms of turnaround time, less errors and reliability.

Objective The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). Methods This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. Results We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. Conclusion Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29–90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Aim: Human parechovirus (HPeV) is one of the major causes of acute gastroenteritis in children. Materials & methods: Stool specimens (n = 250) were collected from children aged ≤3 years during 2018–2019. HPeV RNA was detected by reverse transcription-PCR and genotyping by VP1 gene, Rotavirus (RV) screened by ELISA. Results: HPeV was detected in 12% of the cases. The children under 6-months old (64.2%) were a sensitive group and HPeV was more prevalent during January–February (73.3%). The co-infection of HPeV with RV was 50%. All of the sequenced samples belong to the HPeV-1 genotype. Conclusion: HPeV-1 is one of the major causes of acute viral gastroenteritis in children and the co-infection of RV can be an additional infection in some cases.

Rotavirus and norovirus are well-known causes of viral infectious diarrhea. There are few reports on diarrhea caused by other viruses in Korea, although cases of gastroenteritis attributable to other viruses are increasing worldwide. The aims of this study were to detect various causes of viral diarrhea and to investigate their prevalence. A total of 801 fecal specimens submitted to a clinical microbiology laboratory for the detection of diarrheal viruses were included. We sought to detect rotavirus A/B/C, adenovirus, astrovirus, norovirus GI/GII, sapovirus, Aichi virus, human parechovirus, enterovirus, human cosavirus, human bocavirus, and Saffold virus using multiplex reverse transcription polymerase chain reaction (RT-PCR). At least one diarrheal virus was detected in 223 (27.8%) fecal specimens. Among them, two viruses were detected in 11 specimens. Rotavirus A was most common (17.1%; N = 137), followed by norovirus GII (5.0%; N = 40), enterovirus (4.2%; N = 34), adenovirus (1.0%; N = 8), astrovirus (1.0%; N = 8), human parechovirus (0.6%; N = 5), and human bocavirus (0.2%; N = 2). Rotaviruses B and C, norovirus GI, sapovirus, Aichi virus, human cosavirus, and Saffold virus were not detected. We confirmed that various diarrheal viruses can be detected in fecal specimens. We must consider the possibility of viruses other than rotavirus and norovirus being present in cases of diarrhea.

Among enteric viruses, rotavirus A (RVA), norovirus (NoV), adenovirus, and astrovirus (AstV) are the major etiological agents associated in acute gastroenteritis. The present study highlights, clinical, epidemiological, and molecular aspects with respect to RVA, NoV, enterovirus (EV), and human parechovirus (HPeVs) in sporadic cases (n = 305) of acute gastroenteritis, Pune (Maharashtra), Western India. Detection of RVA was carried out by enzyme-linked immunosorbent assay, NoV, EV, and HPeVs by reverse transcription PCR. Prevalence of 36.06%, 20.32%, 14.09%, 3.93%, respectively was observed for RVA, EV, HPeVs, and NoV along with coinfections. Infections occurred in children less than 2 years old, with peak infections within 12 months age. The disease severity in RV infections was found high (70.90%) with severe disease, followed by EV (62.9%), NoV (58.33%), and HPeV (44.58%). Predominant strains of RV G1P[8], G2P[4] types with unusual G9P[4], NoV Genogroup II of genotype 4 strains and multiple EV types with EV-B species, E14 and E17 and two novel EV-75, EV-107 types were detected. Circulation of heterogeneous HPeV genotypes (HPeV1-5, 7, 8, 13, 14, 16) with predominance of HPeV-1 was noticed. Changing trends in circulation of a rare HPeV-2 genotype, with emerging and reemerging strains was noted. The study highlights association of RVA, NoV, EV, and HPeV and their mono-infections, genotype distribution, and changing trends in acute gastroenteritis, and added more knowledge on rota and nonrota enteric viruses in acute gastroenteritis. More such studies in rota vaccinated era are required across the country, as Indian rotavirus vaccine has been implemented under the National Immunization program.

Parechoviruses are emerging pathogens of humans often affecting the pediatric age group, with a growing line of evidence implicating them as agents of a broad spectrum of clinical syndromes in adults. However, because many clinicians are not familiar with the manifestation of the infections, they are not included in the list of diagnostic pathogens. Furthermore, due to the indistinguishable feature of the infection compared with other common pathogens, a large number of cases are likely to go unchecked. Some may develop asymptomatic infection and recover without overt clinical disease. In this manuscript, we reviewed available literature on parechovirus infection in adult and summarized information relating to epidemiology, clinical manifestation, laboratory diagnosis, and therapeutics. The information provided should help in early case detection and support an evidence-based clinical decision.

Biological evolution of the microbiome continually drives the emergence of human viral pathogens, a subset of which attack the nervous system. The sheer number of pathogens that have appeared, along with their abundance in the environment, demand our attention. For the most part, our innate and adaptive immune systems have successfully protected us from infection; however, in the past 5 decades, through pathogen mutation and ecosystem disruption, a dozen viruses emerged to cause significant neurologic disease. Most of these pathogens have come from sylvatic reservoirs having made the energetically difficult, and fortuitously rare, jump into humans. But the human microbiome is also replete with agents already adapted to the host that need only minor mutations to create neurotropic/toxic agents. While each host/virus symbiosis is unique, this review examines virologic and immunologic principles that govern the pathogenesis of different viral CNS infections that were described in the past 50 years (Influenza, West Nile Virus, Zika, Rift Valley Fever Virus, Hendra/Nipah, Enterovirus-A71/-D68, Human parechovirus, HIV, and SARS-CoV). Knowledge of these pathogens provides us the opportunity to respond and mitigate infection while at the same time prepare for inevitable arrival of unknown agents.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in‐house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV‐A71, echovirus 30, coxsackie A virus 21, and EV‐D68), HPeV3, and specificity controls. Reported results from 48 in‐house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 µL) transcripts. In‐house assays showed significantly greater detection frequencies of the low copy (10 copies/5 µL) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 × 10−5). EV‐specific PCRs showed low cross‐reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in‐house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point‐of‐care tests. © 2019 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The majority of parechovirus A type 5 (PeV-A5) infections have been reported in patients with gastrointestinal syndromes. In contrast, a sepsis-like illness associated with PeV-A5 infection has been reported only anecdotally. Herein, we report the first case in Italy of a PeV-A5 neurological infection presenting in a neonate with a sepsis-like syndrome. The patient, a healthy male infant born at 41 weeks of gestation, was highly distressed and inconsolable, and had been crying persistently, with poor breastfeeding, since the previous day. From day 2 to day 4, the newborn was feverish with mild irritability; breastfeeding was preserved and regularly supported. His clinical condition progressively improved, with defervescence on day 4. He was discharged after 7 days, and neurological examination results indicated only mild impairment in visual fixation and vertical eye tracking and mild axial hypotonia. The Italian PeV-A5 strain was phylogenetically related to three strains detected in Denmark in 2012, as well as to one detected in Australia and one in Greece in 2015, with an average nucleotide identity of 97.9% (range 95.9–100.0%). Enterovirus/PeV infection in the newborn should be ruled out in cases of infants with unexplained fever and/or a sepsis-like syndrome and/or meningoencephalitis. An aetiological diagnosis is essential to avoid the unnecessary administration of antibiotics and to plan long-term follow-up until schooling. Keywords: Neonatal infections, Human parechovirus type 5, CSF, Molecular characterization, CNS infection, Phylogenetic analysis

Human parechoviruses (HPeVs) are increasingly recognized pathogens that cause mild-to-life-threatening diseases in children and adults. Recently, nucleic acid detection has become the mainstream method for pathogen detection. However, virusisolation is still important for virus detection and for further virologic characterization studies as well as securing bioresources. We recently explored conventional cell lines suitable for human sapovirus isolation, and unintentionally identified a human duodenum cell line, HuTu80, that supported the efficient growth of human Parechovirus Type 3 (HPeV-3) with clear cytopathic effects (CPE). Then, we confirmed that all representative prototype HPeV Type 1-6 strains were efficiently propagated in HuTu80 with clear CPE within 4 days. Another human ileocecal cell line, HCT-8 (HRT-18) also supports HPeV propagation except HPeV-3. Titers in HuTu80 and HCT-8 reached approximately 6.83-8.83 and 6.50-8.17 log10 TCID50/50 μL, respectively, when inoculated with multiplicity of infection 0.0025. Previously reported cell lines likely support HPeV Types 1-6 with different efficiency, especially HPeV-3. In summary, HuTu80 can be used as an additional cell line for HPeV isolation and propagation with clear CPE, to produce high titer viruses, and in neutralization assays.

Human parechovirus (PeV-A), one of the species within the Picornaviridae family, is known to cause disease in humans. The most commonly detected genotypes are PeV-A1, associated with mild gastrointestinal disease in young children, and PeV-A3, linked to severe disease with neurological symptoms in neonates. As PeV-A are detectable in stool and nasopharyngeal samples, entry is speculated to occur via the respiratory and gastro-intestinal routes. In this study, we characterized PeV-A1 and PeV-A3 replication and tropism in the intestinal epithelium using a primary 2D model based on human fetal enteroids. This model was permissive to infection with lab-adapted strains and clinical isolates of PeV-A1, but for PeV-A3, infection could only be established with clinical isolates. Replication was highest with infection established from the basolateral side with apical shedding for both genotypes. Compared to PeV-A1, replication kinetics of PeV-A3 were slower. Interestingly, there was a difference in cell tropism with PeV-A1 infecting both Paneth cells and enterocytes, while PeV-A3 infected mainly goblet cells. This difference in cell tropism may explain the difference in replication kinetics and associated disease in humans.

Background Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. Methods We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. Results Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. Conclusions Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.

Parechovirus A (PeV-A) has emerged as a leading cause of infant central nervous system (CNS) infections. Risk factors associated with infant acquisition of PeV-A are not well understood.We conducted prospective PeV-A/enterovirus (EV) CNS infection surveillance, enrolling 461 hospitalized infants90 days old who underwent sepsis evaluations and lumbar puncture during 2011-2012. Infants were grouped by RT-PCR detection of PeV-A, EV, or neither virus (Neg) in CSF. We collected demographic/clinical data and tested specimens from all infants. For 427 mothers, we collected demographic/clinical data and evaluated PeV-A3 and EV shedding, and PeV-A3 neutralizing antibody for 147 mothers.PeV-A was detected in 40 infants (8.7%), 4 in 2011 and 36 in 2012. EV was detected in 35 infants (7.6%), 16 in 2011, and 19 in 2012. PeV-A infected infants presented with irritability, abdominal discomfort, fever, and tachycardia, plus both lymphopenia and absence of CSF pleocytosis which help differentiate PeV-A from EV CNS infection. PeV-A was detected in 9/427 maternal throat swabs; eight of their infants also had PeV-A CNS infection. Infants whose mothers had PeV-A3-positive throat swabs were more likely to be PeV-A3-positive than infants whose mothers had negative throat swabs (relative risk [RR], 13.4 [95% CI, 8.6 - 20.7]). Maternal PeV-A3 seropositivity decreased with increasing maternal age. Mothers of PeV-A-positive infants had lower median PeV-A3 neutralizing titers and were more likely seronegative.Maternal viral shedding, serostatus and neutralization titers appear to be important factors in infant PeV-A3 CNS infections.

In Greece, data for human parechoviruses (HPeVs) are scarce and our aim was to conduct a large scale study to determine for the first time their occurrence. Under the spectrum of surveillance, we retrospectively screened stool specimens obtained from 71 children with acute flaccid paralysis (AFP) symptoms and from 311 individuals in high-risk population groups such as children living in bad sanitation conditions for HPeVs presence by rRT-PCR targeting the 5' UTR. All positive samples were then genotyped by targeting the HPeVs VP1 region. Totally, 15/311 (5%) stool samples from children living in bad sanitation conditions and 4/71 (6%) from the non polio AFP children were positive for HPeVs. Sequencing analysis revealed that genotypes HPeV1 (n = 4/15), HPeV5 (n = 2/15), and HPeV6 (n = 2/15) were circulating among Roma children population whereas HPeV1 (n = 1/4) and HPeV5 (n = 1/4) were circulating in children with AFP-like symptoms. We did not obtain a seasonality motive among HPeV1 or HPeV5 genotypes whereas HPeV6 was detected only in July. Phylogenetic analysis showed that Greek HPeVs strains are clustered together with HPeV strains circulating in other European countries during the same period. We describe the presence of HPeVs in Greece, and we enforce that their diagnosis should be considered in children with neurological outcome such as non-polio AFP.

Human parechovirus infection is an increasingly recognized cause of neonatal meningoencephalitis. We describe characteristic clinical features and brain MR imaging abnormalities of human parechovirus meningoencephalitis in 6 infants. When corroborated by increasingly available polymerase chain reaction-based testing of the CSF, the distinctive MR imaging appearance may yield a specific diagnosis that obviates costly and time-consuming further clinical evaluation. In our study, infants with human parechovirus presented in the first 35 days of life with seizures, irritability, and sepsis. MR imaging consistently demonstrated low diffusivity within the thalami, corpus callosum, and subcortical white matter with a frontoparietal predominance. T1 and T2 shortening connoting white matter injury along the deep medullary veins suggests venous ischemia as an alternative potential pathogenetic mechanism to direct neuroaxonal injury.

Aim Human parechoviruses (HPeV) are responsible for fever without a source (FWS), sepsis-like illness and encephalitis in neonates and children under 3 months of age. Short-term outcome is generally good, but there is great concern about medium and long- term outcome of infants after HPeV infection. The aim of this study is to assess the medium-term outcome in infants following HPeV infection without encephalitis. Methods Patients who suffered HPeV infection involving cerebrospinal fluid were evaluated twice using Ages and Stages Questionnaire-3 (ASQ-3). The first evaluation was conducted at least one year after the infection and the second one year later. Results Sixteen patients were evaluated in the first assessment, and three of them presented mild alterations in motor function domains. Moreover, hypotonia was observed in the neurologic exam in one case, and hemiparesis in another case. In the second assessment fifteen patients were included, and only the patient with hemiparesis continued presenting gross motor disfunction, with complete recovery of the remaining patients. Interpretation We have observed a good medium-term prognosis in infants after HPeV infections, with improvement of mild motor alterations after at-home intervention. Infants who suffer HPeV infection without encephalitis seem to have a better prognosis than those with encephalitis.

Little is known about human parechovirus (HPeV) infection in Thailand. The genotype distribution of HPeV strains in children admitted to hospitals with acute gastroenteritis was investigated using polymerase chain reaction (PCR) and nucleotide sequencing of the VP1 region as the detection and genotype identification methods, respectively. Of a total of 2,002 stool samples, 49 (2.4%) were positive for HPeV. Of these, HPeV-1 was the most predominant genotype (40.8%), followed by HPeV-3 (16.3%) and HPeV-14 (16.3%), while HPeV-5, -6, -2, -4, and -8 strains were less frequently detected, at 10.2%, 8.2%, 2%, 2%, and 2%, respectively. HPeV infections were detected throughout the year with the biannual peaks of infection in the rainy (Jun-Jul-Aug) and winter (Nov-Dec-Jan) months in Thailand. Based on VP1 amino acid sequence alignment, the arginyl-glycyl-aspartic acid (RGD) motif was found in HPeV-1, -2, -4, and -6 strains. Additionally, an amino acid insertion at the N-terminus of VP1 was observed in HPeV-4 and HPeV-5 strains. Phylogenetic analysis revealed that small clades of HPeV-1 and HPeV-3 strains emerged in 2016 and 2015, respectively, and dominated in the year of their emergence. The HPeV strains detected in Thailand in this study were most closely related to reference strains from Asia and Europe. The evolutionary rate of HPeV strains was 2.87 × 10−4 (95% highest posterior density (HPD) 0.10-6.14 × 10−4) substitutions/site/year. These findings provide information about the genetic diversity and evolutionary dynamics of HPeV genotypes circulating in pediatric patients with acute gastroenteritis in Thailand.

Human parechoviruses (HPeV) are ubiquitous and mainly occur in early infancy. They are known to cause various clinical manifestations including acute gastroenteritis. To gain insight into the diversity of circulating HPeV genotypes, stool samples from patients (n = 539) with clinical signs of infectious gastroenteritis which showed negative results for other common viral and bacterial enteric pathogens were obtained during three years, 2008 to 2010. Real-time RT-PCR showed HPeV RNA in 34 (6.3%) of the samples. The HPeV detection rate was highest (8.8%) in samples derived from infants and young children under the age of two years. Genotyping was based on VP3/VP1 junction nucleic acid sequences and revealed predominant HPeV-1B (n = 16) and HPeV-3 (n = 12) strains. Those prevailed minor HPeV-6 (n = 3) as well as HPeV-2, −4 and −5 (n = 1, each) strains. To ascertain the assigned HPeV-2 genotype of uncommon strain LPZ04-2008, analysis of complete coding sequences was performed. In complete VP1 analysis strain LPZ04-2008 showed 81.2% nucleic acid identity with HPeV-2 reference strain Williamson. In phylogenetic analysis VP1 of strain LPZ04–2008 clustered with a recent HPeV-2 strain from the UK. Regarding clinical manifestations, severe disease occurred HPeV-1B, −3 and − 6 infections. In conclusion, this paper a high genetic diversity of HPeV in stool samples, including rare strains. The investigation adds data on the whole coding sequences of the rare HPeV-2 strain. Genotyping results confirm previously reported association of more severe illness with HPeV-3 and HPeV-1B strains.

Abstract: Introduction: Most human parechovirus (HPeV, family Picornaviridae) infections are asymptomatic but may cause gastroenteritis in children. New reports show that HPeVs can be associated with severe central nervous system symptoms and sepsis-like syndromes in infants. The clinical significance of HPeVs in Hungary has not been investigated before. Aim: The aim of this study was to detect genotype HPeV in faecal samples of children and analysis of the clinical symptoms. Method: For the detection and genotyping of HPeV strains, reverse transcription–polymerase chain reaction and sequencing methods were used from faecal samples of children with gastroenteritis divided into three groups: group A) hospitalised children younger than 10 years (n = 75); group B) 0–12 months infants (n = 237) and group C) children less than 18 years of age with sepsis-like/neurological symptoms (n = 105) were tested. Results: Three HPeV positive samples (3/75, 4%) were found in group A, two of them belong to the HPeV type 1, the third was non-typeable. All positive samples were from infants of 7 to 11 months of age. In group B, HPeV was detected in 6.8% (16/237) of the samples. Five were HPeV1, six were HPeV3 and five were non-typeable. While most of the infants with HPeV1 (4/5) did not require hospitalisation, 83% of the HPeV3 infected infants (5/6) did. Five (4.8%) HPeV strains detected from children less than 18 years of age with sepsis-like/neurological symptoms (group C) belonged to HPeV1 (three) and HPeV3 (two). All positive samples were from hospitalised infants less than 2 months of age. Conclusion: HPeV1 infections are less severe in infants than HPeV3 infections. The leading symptom of HPeV1 was diarrhoea, although in infants less than 1–2 months neurological symptoms (somnolence, lassitude) were also present. HPeV3 infections were more common among newborns. The main symptoms of severe HPeV3 infection are: gastroenteritis (7/8), fever ≥38 °C (6/7), loss of appetite (6/7), rash (4/7), somnolence/lassitude (3/7), sepsis-like syndrome (3/7) and respiratory symptoms (2/7). Orv Hetil. 2019; 160(10): 386–395.

Human parechoviruses belong to the Picornaviridae family and are classified into 17 genotypes. Recently, it has been reported that human parechovirus genotype 3 is an important cause of severe infections, including sepsis-like illness and encephalitis, especially in newborns and infants younger than 3 months. There are also reports that human parechovirus genotype 3 infections with central nervous system symptoms lead to high rates of neurological sequelae and death. Here, we report a case of a previously healthy 1-month-old girl who developed encephalitis related to human parechovirus genotype 3 and had a favorable outcome. The patient presented septicemic symptoms, including fever, tachycardia, tachypnea with retractions and seizures without an elevated inflammatory response. She lacked cerebrospinal fluid pleocytosis but had hypercytokinemia. Brain magnetic resonance imaging and electroencephalography showed abnormal findings. Together, these findings strongly suggested acute encephalopathy. She underwent emergency intubation for respiratory failure and mechanical ventilation was started. Intravenous phenobarbital injection was performed to prevent convulsion. She was treated using intravenous immunoglobulin with methylprednisolone pulse therapy. As of 2 years after discharge, her growth development is equivalent to her age and she has had no clinical epileptic seizures. In this case, human parechovirus genotype 3 was detected from pharyngeal swabs, stool, cerebrospinal fluid and blood by polymerase chain reaction assay. The patient was diagnosed definitively with encephalitis related to human parechovirus genotype 3. The symptoms that we observed should be considered for the differential diagnosis of human parechovirus infection. When a patient is suspected of having encephalitis related to human parechovirus, treatment including intravenous immunoglobulin and corticosteroid must be started as soon as possible to prevent neurodevelopmental sequelae. Int J Clin Pediatr. 2019;8(2):37-40 doi: https://doi.org/10.14740/ijcp333

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood. He died five days after his initial presentation. Neuropathologic examination demonstrated multicystic encephalomalacia (ME). This case report confirms that white matter pathology is dominant in HPeV3 infection. A unique feature, of HPeV encephalomalacia is absence of CSF pleocytosis and minimal inflammation in the meninges. The findings permit comment on the pathogenesis of brain injury by this virus.

Background The pathogens involved in central nervous system (CNS) infections are various, such as viruses, bacteria, and fungi, so a syndromic approach can be required. In addition, since their rapid and accurate detection is very crucial, molecular diagnostics using cerebrospinal fluid is becoming the emerging standard method. Methods The study was conducted retrospectively to identify the incidence and distribution patterns of the pathogens according to gender, age, season, and month and to analyze their codetection from August 2017 to July 2020. It was also conducted to investigate turn-around times (TATs) according to the detection method. The detection methods were FilmArray® Meningitis/Encephalitis (M/E) method (FilmArray), Cepheid® Xpert EV assay (Xpert), and Multiplex PCR method for five species of bacteria. Results The overall incidence for at least one pathogen was 13.9% (346/2,496). The highest incidence was shown in age group 4 (3 - 6 years), with 27.4%. The detection rates by FilmArray, Xpert, and Multiplex PCR method were 39.8%, 41.7%, and 0.4%, respectively. Enterovirus (EV) showed the highest incidence rate, which accounted for 37.0%. The distribution of the pathogens according to the age groups were the highest in age group 4, with 47.5% (168/354), followed by 27.4% (97/354) in age group 5. Of the ten cases in which bacteria were detected, S. agalactiae accounted for 60.0% (6/10), most of which occurred in age group 1. E. coli K1, L. monocytogenes, and N. meningitidis were not detected. In the viral distribution, EV accounted for the highest proportion in all age groups. The overall proportion of EV accounted for 87.6% (310/354), followed by human parechovirus with 2.8% (10/354). The most commonly detected season was summer, comprising 75.1%. A total of eight cases of co-detection with two pathogens accounted for 1.6% (8/507) in FilmArray. In FilmArray, all TATs were found to be shorter than Xpert. Conclusions The information on the incidence and distribution patterns of the pathogens causing CNS infections and their rapid detection are critically important to clinicians in the management of immunocompromised patients, elderly, and children. The expeditious molecular diagnostics for these pathogens would be valuable in medical decisions by clinicians.

Parechoviruses (PeVs) are common viruses that cause mild gastrointestinal or respiratory symptoms to severe central nervous system infections. In infants, parechovirus infection is one of the leading causes of life-threatening viral disease. High-quality antibodies with broad binding specificities are essential to improve accurate parechovirus diagnosis in diagnostic laboratories. Such antibodies have potential in the development of rapid antigen detection assay against PeVs. In the present study, VP4 and VP2 genes from human parechovirus A1 (PeV-A1) were cloned and VP0 fusion protein produced to develop monoclonal antibodies against PeVs. Two pan-parechovirus antibodies, one IgG and one IgM isotype, were isolated. The properties of IgG1/κ monoclonal (designated as Mab-PAR-1) was studied further. Mab-PAR-1 was shown to be functional in western blot against denatured recombinant protein and viral particles. In immunofluorescence assay, the antibody tested positive for nineteen PeV-A1 isolates while showing no cross-reactivity to fourteen entero- and rhinovirus types. In addition, Mab-PAR-1 showed positive reactivity against five other cultivable parechovirus types 2-6. A unique Mab-PAR-1 epitope located in the junction of the three capsid proteins VP0, VP1, and VP3 was identified using a peptide library screen. This study demonstrates that PeV-A1-VP0 protein is functional antigen for developing monoclonal antibody for diagnosis of broad range of parechovirus infections.

Human parechovirus (HPeV) is one of the members of the family Picornaviridae that has been associated with fever of unknown origin, gastroenteritis, clinical sepsis, meningitis, or encephalitis in very young infants. HPeV detection is not routinely performed in most clinical microbiology laboratories in Argentina and, therefore, its real prevalence is unknown. We here report three cases of HPeV CNS infection that presented to our hospital with different clinical features after the implementation of a multiplex PCR meningitis/encephalitis panel. Molecular diagnostic techniques could help improve patient care and understand the real prevalence of this infection in Argentina.

Human parechoviruses (HPeVs) are human pathogens that usually cause diseases ranging from rash to neonatal sepsis in young children. HPeV1 and HPeV3 are the most frequently reported genotypes and their three-dimensional structures have been determined. However, there is a lack of systematic research on the antigenic epitopes of HPeVs, which are useful for understanding virus-receptor interactions, developing antiviral agents or molecular diagnostic tools, and monitoring antigenic evolution. Thus, we systematically predicted and compared the conformational epitopes of HPeV1 and HPeV3 using bioinformatics methods in the study. The results showed that both epitopes clustered into three sites (sites 1, 2 and 3). Site 1 was located on the "northern rim" near the fivefold vertex; site 2 was on the "puff"; and site 3 was divided into two parts, of which one was located on the "knob" and the other was close to the threefold vertex. The predicted epitopes highly overlapped with the reported antigenic epitopes, which indicated that the prediction results were accurate. Although the distribution positions of the epitopes of HPeV1 and HPeV3 were highly consistent, the residues varied largely and determined the genotypes. Three amino acid residues, VP3-91N, -92H and VP0-257S, were the key residues for monoclonal antibody (mAb) AM28 binding to HPeV1 and were also of great significance in distinguishing HPeV1 and HPeV3. We also found that two residues, VP1-85N and -87D, might affect the capability of mAb AT12-015 to bind to HPeV3.

Human parechovirus 3 (HPeV-3) and enteroviruses (EV) are commonly detected viruses in febrile neonates and young infants and are usually diagnosed by PCR. However, in this population, data on detection rates for samples from different anatomical sites are limited.To determine PCR detection rates for HPeV-3 and EVs in serum and cerebrospinal fluid (CSF) samples from febrile neonates and young infants.This prospective study identified viruses in serum and CSF samples collected from febrile neonates and young infants (age4 months) in Niigata, Japan, during 2014-2018. HPeV-3 or EV infection was defined as a positive quantitative real-time PCR result for the virus in serum or CSF. Genotypes were identified by sequence analyses of the viral protein 1 region.Among 216 patients, we identified 56 HPeV-3-infected (26 %) and 48 EV-infected patients (22 %). All (56/56; 100 %) HPeV-3-infected patients had a positive PCR result for serum, and 49/56 (88 %) had a positive result for CSF. In EV-infected patients, 40/48 (83 %) were positive for serum, and 34/48 (71 %) were positive for CSF, and 22/48 (46 %) were positive for serum (n = 14) or CSF (n = 8). If only a CSF sample had been obtained, 7 (12 %) HPeV-3 infections and 14 (29 %) EV infections would have been undiagnosed. Detection rates in serum and CSF differed by genotype in EV-infected patients.Viral RNA detection rates differed between serum and CSF in HPeV-3- and EV-infected neonates/infants. Combined evaluation of serum and CSF samples is important for accurate viral diagnosis in this population.

Human parechoviruses (HPeVs) are highly common pathogens in children under 2 years of age. Of the 19 distinct HPeV genotypes identified worldwide, HPeV1 is still the most prevalent type associated with respiratory and gastrointestinal symptoms in infants and young children. Pakistan's previous studies have focused only on the detection and partial sequencing of HPeV genotypes. In the present study, we have obtained the complete genomes of 2 HPeV1 strains (PAK419 and PAK663) from children using NGS method on Illumina Hiseq Platform. These samples were collected from children suffering from acute gastroenteritis in Rawalpindi, Pakistan during 2016. The near complete genome sequences obtained for two HPeV1 strains (PAK419 and PAK663) consist of total 6877 nucleotides with a single, large open reading frame (ORF) encoding a polyprotein gene. Phylogenetic analysis showed that both HPeV1 strains exhibited maximum amino acid similarity (97 %) to HPeV1 strains from The Nederlands (2007-863, GQ183034) and clustered closely with this and with other HPeV1 strains isolated from other countries in the world (Ethiopia, Taiwan, Russia and Brazil). A motif of arginine-glycine-aspartic acid (RGD) in the VP1 (Outer capsid protein) C-terminus region that is suggested to help virus entry into the host cell also identified in PAK419 and PAK663. SimPlot analysis revealed that intergenotypic recombination events may have take place in the non-structural region between both HPeV1 strains (PAK419, PAK663), two major strains of HPeV1 (GQ183034 and MG873157) and four minor strains of HPeV4 (AM235750), HPeV7 (EU556224), HPeV15 (MN265386) and HPeV18 (KT879915). The full genome of HPeV1 strains characterized in the current study will provide complete information on these newly isolated strains for further preventive or treatment measures.

Background and Objectives: Severe acute respiratory infections (SARI) remain an important cause for childhood morbid- ity worldwide. We designed a research with the objective of finding the frequency of respiratory viruses, particularly WU and KI polyomaviruses (WUPyV & KIPyV), human coronaviruses (HCoVs), human respiratory syncytial virus (HRSV) and human parechovirus (HPeV) in hospitalized children who were influenza negative. Materials and Methods: Throat swabs were collected from children younger than 5 years who have been hospitalized for SARI and screened for WUPyV, KIPyV, HCoVs, HRSV and HPeV using Real time PCR. Results: A viral pathogen was identified in 23 (11.16%) of 206 hospitalized children with SARI. The rate of virus detection was considerably greater in infants

BACKGROUND: Human parechovirus (HPeV) typically infects young children, and although infection is often asymptomatic, some types (eg, HPeV3) are associated with severe clinical manifestations, including central nervous system infection or sepsis-like syndrome, particularly affecting young infants. The third documented national epidemic of HPeV occurred in Australia in 2017-2018. METHODS: Four public laboratories that perform almost all of the HPeV PCR testing in New South Wales provided data regarding HPeV tests performed from July 1, 2017 to June 30, 2018. Limited demographic and clinical data were obtained from electronic medical records for laboratory test-positive cases that presented to each of the 3 pediatric hospitals in New South Wales. RESULTS: Five hundred eighty-one HPeV-positive samples obtained from 395 cases were included in the analysis. The peak of the outbreak occurred in late November 2017 (approximately 35 new cases each week), with the main HPeV epidemic occurring between the spring and summer months of September 2017 to January 2018; although this seasonality was observed primarily in infants less than 12 months of age. Among the 388 pediatric cases, almost half were younger than 2 months (188; 47%) and only 10 were children older than 2 years. The annualized estimated incidence of laboratory confirmed HPeV infection in children was approximately 142.4 cases per 100,000 children younger than 5 years in New South Wales during the epidemic season. CONCLUSIONS: The large burden of HPeV infection and disease identified in young infants in this and previous Australian studies highlight the need for more comprehensive national surveillance of HPeV infections and improved prevention strategies.

Sepsis-like illness with suspected meningitis or encephalitis is a common reason for using empiric antimicrobial therapy in infants and children. However, in cases of viral meningitis not covered by these antimicrobials, this management is ineffective and due to side effects potentially harmful. A retrospective analysis of cerebrospinal fluid (CSF) multiplex PCRs (Biofire FilmArray®) in children with clinical suspicion of meningitis, encephalitis or sepsis-like illness was performed over the period of 1 year. Subsequently, a subgroup of children (age of 8–84 days of life) diagnosed with viral meningitis (enterovirus, HHV-6, human parechovirus) was compared to an age-matched control group. During the study period, the multiplex PCR panel was performed on 187 individual CSF samples that met the inclusion criteria. About half of the patients (92/187) were less than 1 year of age. In 27 cases (14.4%), the PCR yielded a positive result with the majority (12/27) being indicative of an enteroviral infection. In the age group of 8–84 days of life, 36.4% of the patients had a positive result. When the patients with a PCR positive for a viral agent were compared to an age-matched group of patients, no differences were observed regarding symptoms and laboratory parameters. However, the duration of antimicrobial therapy could be significantly reduced through the use of multiplex PCR. The use of on-site diagnostic multiplex PCR was able to reduce the use of antimicrobials in selected cases. This test can guide clinical decisions earlier during the course of medical care compared to standard diagnostics.

Background: Acute respiratory infection (ARI) is caused by human metapneumovirus (HMPV), respiratory syncytial virus type A and B (RSV-A, RSV-B), human parainfluenza viruses 1, 2, and 3 (HPIV-1, HPIV-2, and HPIV-3), influenza viruses A and B (IfV-A, IfV-B), and human coronaviruses (OC43/HKU1, NL63, 229E) worldwide. Objectives: This study was conducted to assess the causative agents of viral ARI among hospitalized adults by real-time PCR. Methods: Clinical nasopharyngeal swabs of 112 patients including 55 (49.1%) males and 57 (50.89%) females with ARI were analyzed using multiplex real-time RT-PCR. Results: Out of 112 specimens, 61 (54.46%) were positive including 10 (8.9%) for influenza H3N2, one (0.89%) for influenza B, 28 (25%) for RSV-A, 18 (16.07%) for HMPV-A, two (1.78%) for HPIV-1, and three (2.67%) for HPIV-3. Two (1.78%) specimens were positive for two agents, RSV-A/HMPV-A and RSV-A/HPIV-3. The distribution of viral infections was 30 among males (26.78%) and 31 (27.67%) among females (P = 0.862). High frequency of RSV-A infection (25%) and the low frequency of influenza B virus infection (0.89%) were detected among patients. The remaining 51 (45.53%) samples were negative for RSV-B, HMPV-B, IfV-A, HPIV2-4A-4B, and HCoVs (OC43/HKU1, NL63, 229E). Conclusions: The role of other viruses such as human adenoviruses rhinovirus/enterovirus (RV/EV), human bocavirus (HBoV), and human parechovirus (HpeV) was not investigated. Multiplex PCR can be used as a rapid test for the diagnosis of viruses causing acute respiratory infection, which results in decreased length of hospitalization.

This article aims to describe a rare cause of severe encephalitis in 2 cases of infants with signs of intracranial hypertension and severe autonomic dysregulation. The authors conclude that human parechoviruses are becoming a more recognized cause of encephalitis because of the increasing use of rapid detection methods. With early recognition of this clinical entity, improved care can be administered.

Background Human astroviruses have increasingly been identified and are important agents of diarrheal disease, especially in infants and young children. This article presents the real-time polymerase chain reaction TaqMan assay for the detection and quantification of human astrovirus for clinical fecal samples collected from hospitalized children with acute gastroenteritis in Piedmont (northern Italy) from December 2014 to November 2015. Methods A total of 159 fecal specimens from hospitalized children with acute gastroenteritis, previously screened for rotavirus, adenovirus, norovirus, human parechovirus, salivirus and sapovirus, were tested for human astrovirus. Results The most commonly detected virus was norovirus GII (33.8%), followed by rotavirus (21.3%), sapovirus (10.9%), human parechovirus (8%), norovirus GI (6.7%), adenovirus (1%) and salivirus (0.52%). A total of 30 of 159 (18.87%) episodes of acute gastroenteritis were associated with human astrovirus genomic detection. Conclusions Our data showed that the detection rate of astrovirus in diarrheal children (18.87%) was higher than observed in other countries, where they were reported in diarrheal children in 10.3%-0.8% of patients and a mean incidence worldwide of 11%. Our data showed that the detection rate of astrovirus in pediatric gastroenteritis was greater than previously reported in Italy.

Human parechovirus (HPeV) infections in Yokohama City, Japan, were surveyed from 2000 to 2016. The sequence of the VP1 region of HPeVs was used to construct a phylogenetic tree and to reveal the putative amino acid (aa) sequences. Phylogenetic analysis showed the presence of 3 genotypes in Yokohama City: HPeV1 (25 specimens), HPeV3 (86 specimens), and HPeV4 (2 specimens). HPeV1 was detected nearly every year, with the highest number detected in 2014. HPeV3 was not detected until 2005, but was detected over a 1- or 3-yr period thereafter. HPeV1 was most prevalent from July to November, whereas HPeV3 peaked in July and August each year. HPeV1 was mainly detected in patients with infectious gastroenteritis or respiratory tract infections. In contrast, 87% of HPeV3-positive cases were in patients less than 2 months of age with a viral-induced fever. An analysis of the aa sequence of VP1 revealed a divergence within the same HPeV genotype, which was useful in analyzing the emergence and re-emergence of HPeV infections during the survey period. These findings suggest that molecular analysis of HPeVs may contribute to a better understanding of its epidemiology.

Enteroviruses (EV) and human parechoviruses (HPeV) are known and emerging cause of sepsis-like illnesses in infants; however, testing is not yet routine. We retrospectively evaluated the number of diagnosed EV/HPeV infections in children under the age of 5 years who presented with sepsis-like illness or meningitis in Cornwall, UK, before and after routine implementation of viral screening of cerebrospinal fluid samples. During the 4-year period prior to routine testing, we identified 20 cases of EV meningitis and no cases of HPeV. In the year after introduction of routine screening, 27 cases of EV and 14 cases of HPeV were identified in 1 year. The majority of EV/HPeV infections occurred among children under 3 months old between May and August. Clinical and laboratory characteristics of EV and HPeV infections were mostly indistinguishable. We found that CSF pleocytosis and biochemistry-based testing strategy could miss 48.1 and 78.5% of EV and HPeV cases, respectively. With routine viral screening, the mean length of hospital stay (3.8 vs 5.9 days, P 0.001) and antibiotic days (2.8 vs 4.7 days, P 0.001) were significantly reduced in EV/HPeV-positive cases compared to a similar cohort without any detectable microbial aetiology.Routine EV and HPeV testing of CSF samples in children has the potential to reduce length of stay and antibiotic use. What is Known: • EV and HPeV are frequent cause of meningitis and sepsis-like illness among young children. • There is increasing evidence supporting routine EV and HPeV testing of paediatric CSF. What is New: • Outcome of routine EV and HPeV testing in Cornwall, UK. • The value of testing all paediatric CSF without any screening criteria. • A rapid diagnosis of EV/HPeV can significantly reduce length of hospital stay and unnecessary antibiotics.

A previously healthy 6-year-old boy was admitted to hospital with hypotonia and hyposthenia of lower limbs. Electromyography and slow motor nerve conduction velocity test identified a lower limb acute motor axonal neuropathy. Brain and spinal cord magnetic resonance imaging demonstrated multifocal cortical gray matter lesions in both cerebral hemispheres consistent with gray matter acute disseminated encephalitis otherwise with viral/Mycoplasma pneumoniae encephalitis, and signs of involvement of anterior nerve roots of the cauda equina consistent with Guillain-Barré syndrome. The patient resulted negative to routinely bacterial and viral investigations but positive to human parechovirus that sequence analyses confirmed as type 6. Intravenous immunoglobulins and methylprednisolone treatment were administered but did not relieve the symptoms of Guillain-Barré syndrome. The disease improved gradually over the next 3-month follow-up with a complete remission of both central and peripheral nervous system symptoms.

Background Hand, foot and mouth disease (HFMD) is caused mostly by enteroviruses. However, other viral agents also can cause similar syndromes, and hence, the infections they cause are often misdiagnosed clinically. To determine non-enterovirus etiologic agents in HFMD-like cases, we screened enterovirus-negative samples collected from the patients who were clinically diagnosed as HFMD in China. Methods Two hundred enterovirus-negative samples were collected previously in Wenzhou city of Zhejiang province, China. Both high throughput sequencing and RT-PCR were used to screen viral agents. In addition, their clinical features were analyzed. Results Norovirus (NoV) and human parechovirus (HPeV) were identified from 22 (11.00%) and 9 (4.50%) samples, respectively. In addition, the complete genome sequences were recovered from 4 NoV-positive samples, and the VP1/3Dpol gene sequences were recovered from 5 HPeV-positive samples. Phylogenetic analyses of the NoV sequences revealed that they were closely related to those circulated in other regions of China. Notably, 4 genotypes of HPeVs, including HPeV-1, HPeV-4, HPeV-5 and HPeV-14, were found, indicating high genetic diversity of the virus. Frequent recombination between various genotypes was also observed in the HPeVs. Although most of the patients presented with the clinical features of HFMD, 4 patients infected with NoV GII.4 and 3 patients infected with HPeV-1 (1) and HPeV-4 (2) were characterized with diarrhea. Finally, tonsillitis, convulsion and granulocytopenia were observed in 1 NoV GII.4 patient, while liver dysfunction was found in 1 NoV GII.17 patient. Conclusions These data reveal the variety of agents in the cases clinically diagnosed as HFMD.

Many studies show the involvement of Human Parechovirus (HPeV) especially HPeV3 with central nervous system (CNS) infection in young infants. The current study analysed the presence of HPeV in cerebrospinal fluid (CSF) to understand the epidemiological behaviour of parechoviruses and to examine their clinical associations in Albaha, Saudi Arabia. Real-time RT-PCR assay targeting the viral protein 1 (VP1) region was performed on RNA extracts of CSF specimens collected from young infants attending the tertiary care hospital at Albaha. None of the samples analysed showed positivity for HPeVs presence. Suboptimal biological sample, the seasonal pattern of HPeVs infections and use of CSF only as the biological specimen might be some plausible reasons for the negative finding. Present study is the first such attempt in Saudi Arabia and thus it is pertinent that more stringent future studies using biological specimen of varying origins must be conducted to analyse the presence of HPeVs associated with asymptomatic infections or mild disease to severe disease symptoms in neonates and infants especially under the age of 3 months, before ruling out Human Parechovirus (HPeV) presence.

Epidemics of human parechovirus (HPeV) causing disease in young children have occurred every 2 years in Australia since 2013. HPeV genotype 3 caused the epidemic from late 2017 to early 2018. Most HPeV infections cause no or mild symptoms including gastroenteritis or influenza-like illness. Characteristically, young infants present with fever, irritability and on occasions a diffuse rash ("red, hot and angry" babies). Severe disease can manifest as meningoencephalitis, seizures or sepsis-like presentations (including septic shock), or less common presentations including signs of surgical abdomen. Testing for HPeV by specific molecular tests is indicated in children younger than 6 months of age with characteristic presentations without another confirmed diagnosis including febrile illnesses with other suggestive features (eg, rash, seizures), sepsis syndromes (including shock), and suspected meningoencephalitis (which may be detected by magnetic resonance imaging only). There are no effective antiviral therapies. Treatment is primarily supportive, including management of complications. Some infants with severe HPeV infection may have adverse neurodevelopment. Follow-up by a paediatrician is recommended.

Introduction: Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever without source (FWS), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. Patients and methods: A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FWS (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. Results: Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FWS (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. Conclusions: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FWS and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections. Resumen: Introducción: Los parechovirus humanos (HPeV) son virus de la familia Picornaviridae, recientemente descritos, a los que se atribuyen cuadros de fiebre sin foco (FSF), sepsis clínica, gastroenteritis, meningitis o encefalitis fundamentalmente en lactantes pequeños. Nuestro objetivo fue describir la epidemiología y las características clínicas de las infecciones por HPeV en nuestro medio. Pacientes y métodos: Estudio multicéntrico prospectivo, llevado a cabo en 12 hospitales a nivel nacional, entre 2013-2015, en niños 3 meses. Todos los pacientes presentaron fiebre, el 45% irritabilidad, el 18,6% exantema y el 14% diarrea. No se observa ninguna alteración específica en las pruebas bioquímicas. El diagnóstico final más frecuente fue FSF (61%) seguido de sepsis clínica (29%). Aunque un 29% de los niños precisaron ingreso en cuidados intensivos, solo un paciente presentó secuelas. Conclusiones: Los HPeV circulan en nuestro país, afectando fundamentalmente a lactantes < 2 meses y se asocian a FSF y sepsis clínica, con un predominio en primavera y verano. Sería de interés implementar las técnicas moleculares de diagnóstico en todos los hospitales para reconocer y manejar adecuadamente estas infecciones.

Background Human parechovirus (HPeV) and human non-polio enterovirus (EV) are important causes of fever without sources (FWS) in young infants. Their prevalence and clinical characteristics are largely unknown in Asian countries. This study was conducted to elucidate the epidemiology and clinical characteristics of HPeV and EV infections in febrile young infants in Japan. Methods During February 2010 – August 2015, we obtained 53 stool, 44 throat swab, and 20 cerebrospinal fluid (CSF) samples from 56 infants (

Background Parechoviruses (HPeV) are endemic seasonal pathogens detected from the respiratory tract, gut, blood and central nervous system (CNS) of children and adults, sometimes in conjunction with a range of acute illnesses. HPeV CNS infection may lead to neurodevelopmental sequelae, especially following infection by HPeV-3, hence screening and genotyping are important to inform epidemiology, aetiology and prognosis. Objectives To identify and characterise HPeVs circulating during an outbreak between November 2013 and April 2014 in Queensland, Australia. Study design To perform PCR-based screening and comparative nucleotide sequence analysis on samples from children with clinically suspected infections submitted to a research laboratory for HPeV investigations. Results HPeVs were detected among 25/62 samples, identified as HPeV-3 from 23 that could be genotyped. These variants closely matched those which have occurred worldwide and in other States of Australia. Conclusions The inclusion of PCR-based HPeV testing is not systematically applied but should be considered essential for children under 3 months of age with CNS symptoms as should long-term follow-up of severe sepsis-like cases.

We describe the first 2 cases from the United States, of human parechovirus infection in infants manifesting a distinct rash of the hands and feet. We propose the term "Mittens and Booties Syndrome" and provide a review of the literature of all published cases.

Background Little is known on human parechovirus (HPeV) infections in Africa. Objectives We aimed to determine the prevalence, genetic diversity, and association with diarrhea of HPeV in Ghanaian children. Study design A total of 682 stool samples from a pediatric case-control study on causes of diarrhea collected in 2007–2008 were used. Laboratory analysis included HPeV real-time RT-PCR and sequencing partial viral protein (VP) 1 gene region of HPeV. In addition, data on co-infections using the xTAG Gastrointestinal Pathogen Panel were available. Results Overall, a prevalence of 24% was found and 14 different HPeV types were detected. Phylogenetic analysis of the VP1 region indicated a novel type tentatively designated as HPeV-18. No association with diarrhea was found (OR = 0.8; 95% CI: 0.5–1.1), and HPeV viral concentrations were not different among cases and controls. No seasonal pattern was observed. HPeV-positive cases displayed a slightly higher chance of co-infections. Conclusions A high prevalence and genetic diversity of HPeV including novel types was found by sequencing partial VP 1 region. HPeV was not associated with diarrheal disease in this pediatric population and the high number of co-infection suggests transient colonization without clinical relevance.

Parechovirus A (PeV-A), previously known as human parechovirus, is a common pathogen in children that can cause respiratory and gastrointestinal diseases as well as severe neurological disease. Take advantage of our previous findings on the genetic diversity of PeV-A circulating in Japanese children with acute gastroenteritis (AGE), this study was conducted to investigate the genetic diversity of PeV-A isolated from children with AGE in Japan as well as their clinical symptoms. Of 1070 stool samples collected from Japanese infants and children with AGE during the 2-year period from July 2016 to June 2018, 76 were positive for PeV-A by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and were subjected to genotyping based on viral protein 1 (VP1) sequences. Five different PeV-A genotypes including PeV-A1B, −A2, −A3, −A4, and -A6 were detected with predominant of PeV-A1 clade B genotype. This study revealed a high genetic diversity of PeV-A circulating in Japanese infants and children with AGE and the PeV-A2, a rare genotype, was detected for the first time in Japan in patients with AGE. The clinical symptoms observed in these patients included diarrhea, vomiting, fever, cough, rhinorrhea, and dehydration.