Human Parechovirus Genotypes Research Articles

Detection and genetic diversity of parechoviruses in children with acute flaccid paralysis in Cameroon.

Human Parechoviruses (HPeVs) have rarely been considered in the virological investigation of Acute Flacid Paralysis (AFP) cases in Africa, where enteric infections are very common. This study investigated the prevalence and genetic diversity of HPeV in 200 children aged ≤ 15 years with AFP in Cameroon from 2018 to 2019. HPeVs were detected in their faecal RNA using 5'-untranslated real-time RT-PCR. Detected HPeVs were typed by phylogenetic comparison with homologous sequences from homotypic reference strains. Overall, HPeV RNA was detected in 11.0% (22/200) of the 200 stool samples tested. Twelve HPeVs were successfully sequenced and reliably assigned to HPeV-A1, A4, A5, A10, A14, A15, A17 and A18 genotypes. Phylogenetic analyses revealed a high genetic variability among the studied HPeVs, as well as between the studied HPeVs and their previously reported counterparts from Cameroon in 2014. These findings suggest that different HPeV genotypes co-circulate in Cameroon without documented epidemics.

MYADM binds human parechovirus 1 and is essential for viral entry

Human parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we show that MYADM binds to PeV-A1 particles via its fourth extracellular loop, and we identify critical amino acid residues within the loop that mediate binding and infection. The demonstrated interaction between MYADM and PeV-A1, and its importance specifically for viral entry, suggest that MYADM is a virus receptor. Knockout of MYADM does not reduce PeV-A1 attachment to cells pointing to a role at the post-attachment stage. Our study suggests that MYADM is a multi-genotype receptor for human parechoviruses with potential as an antiviral target to combat disease associated with emerging parechoviruses.

The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

Clinical, epidemiological, and molecular aspects of picornaviruses (entero, parecho) in acute gastroenteritis: A study from Pune (Maharashtra), Western India.

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.

Molecular characterization of the complete genome sequence of human Parechovirus 1 in Pakistan

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.

Genotyping of enteroviruses and human parechoviruses highlights their diversity in Northwest Ethiopia.

Enteroviruses (EVs) and human parechoviruses (HPeVs) infections are associated with various forms of disease, including gastroenteritis. As information on the molecular epidemiology of these viruses is limited in Ethiopia, the genetic diversity of EV and HPeV was investigated in the Northwestern part of the country. Of the total 450 stool samples obtained from infants and young children with diarrhea, 157 (34.9%) were positive for EV and 49 (10.9%) for HPeV RNA when tested by real-time reverse transcription polymerase chain reaction. Genotyping was performed by sequencing of the EV VP1 gene and the HPeV VP3/VP1 gene, respectively. Genotyping of EV was successful in 118 samples. Thereof, 82 (69.5%) belonged to non-polio EVs as a broad range of genotypes within species C, B, and A. Sabin polioviruses were found in 36 cases. HPeV sequences were also heterogeneous with a relative dominance of genotype 3. In conclusion, diverse EV and HPeV genotypes were found cocirculating in Northwest Ethiopia. The findings highlight the importance of continuous surveillance of these viruses in Ethiopia.

Early Life Parechovirus Infection Neurodevelopmental Outcomes at 3 Years: A Cohort Study

To investigate the long-term developmental and behavioral outcomes in an established cohort of children hospitalized as infants with human parechovirus (HPeV) infection and sepsis-like illness. The HPeV cohort was composed of children 3years of age after HPeV infection and hospitalization in early infancy that occurred during a well-documented HPeV genotype 3 outbreak in Australia. We assessed neurodevelopmental and behavioral outcomes using the Bayley Scales of Infant and Toddler Development-III and the Child Behavior Checklist. We compared their outcomes with a subsample of healthy control infants drawn from the independently sampled Triple B Pregnancy Cohort Study. Fifty children, with a mean age of 41months, were followed for 3years after hospital admission with HPeV infection. There were 47 children whose original illness was fever without source or sepsis-like illness and 3 who had encephalitis. All children in the HPeV cohort showed age-specific development within the population normal range on the Bayley Scales of Infant and Toddler Development-III. There was no difference in developmental attainment compared with 107 healthy control infants after adjusting for measured confounders. The HPeV cohort showed higher average scores on the Child Behavior Checklist and a higher frequency of clinical range scores compared with healthy controls. Although HPeV sepsis-like illness did not result in neurodevelopmental delay at 3years of age, it was associated with increased behavioral problems compared with healthy controls. The behavioral problems reached a clinical threshold in a minority of children. Results inform clinical management and planning for children after severe HPeV infection in infancy.

Investigation of Respiratory Tract Pathogen Human Parechoviruses in Konya, Turkey

Abstract Objective This study aims to better understand the epidemiological characteristics of parechoviruses and to determine the genotype distribution in Konya, Turkey. Methods In this study, nasal and throat swab samples taken from 1,110 children who were diagnosed with respiratory tract infection (bronchitis, pneumonia, asthmatic bronchitis, and other respiratory diseases) and applied to various pediatric polyclinics of Meram Medical Faculty Hospital, Necmettin Erbakan University between September 2017 and March 2019 were evaluated. Human parechovirus (HPeV) RNA was investigated by multiplex polymerase chain reaction (PCR) in respiratory tract samples. Specific genotypes of the positive samples were identified by real-time PCR amplification of the VP1 region followed by sequence analysis. Results Of the total of 1,110 samples, 4 were positive for HPeV. Of these, HPeV1 was the most predominant genotype (n = 3), followed by HPeV4 (n = 1). HPeV infections were detected throughout the year in Konya, Turkey. Conclusion Although the number of positive samples for HPeV is low, these findings provide information about the genetic diversity and epidemiological of HPeV genotypes circulating in pediatric patients in Turkey. This is the first study to detect prevalence and genotyping of HPeV in respiratory tract infections in Turkey. HPeVs should be considered as causative agents especially in infants with sepsis, meningitis, or encephalitis, and routine testing panels for HPeV detection should be available in hospital laboratories. Further studies using molecular epidemiological methods will be beneficial for identifying genotypes of all HPeVs involved in the etiology and for better monitoring of these infections.

Diversity of human parechovirus in infants and children with acute gastroenteritis in Japan during 2014–2016

A total of 972 stool samples were collected from infants and children with acute gastroenteritis (AGE) in pediatric clinics encompassing six localities (Hokkaido, Tokyo, Shizuoka, Kyoto, Osaka, and Saga) in Japan during the 2-year period from July 2014 to June 2016. Sixty six of the samples (6.8%) were found to be positive for human parechovirus (HPeV) by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and subjected to genotyping based on viral protein 1 (VP1) sequences. Four different HPeV genotypes consisting of HPeV1, -3, -4 and -6 were detected, with HPeV1 clade B being predominant and followed by HPeV3 and -6. The first-time presence of HPeV1 clade A in Japan and rare HPeV4 were noted. This study provides up-to-date information on the genetic diversity of HPeV circulating in Japanese infants and children with AGE.

Molecular epidemiology and genetic diversity of human parechoviruses in children hospitalized with acute diarrhea in Thailand during 2011-2016

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 Parechovirus Infections in Healthy Australian Children During the First 2-Years of Life: A Community-Based Longitudinal Birth Cohort Study

Background: Hospital-based studies identify human parechovirus (HPeV), primarily HPeV3, as important causes of severe infections in young children. However, few community-based studies have been published and the true HPeV infection burden is unknown. We therefore investigated HPeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study. Methods: Australian children (n=158) enrolled in the Observational Research in Childhood Infectious Diseases (ORChID) study were followed from birth until their second birthday. Weekly stool and nasal swabs, and daily symptom diaries, were collected. Swabs were tested for HPeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus co-detections were investigated. Findings: HPeV was detected in 1423/11127 (12·8%) and 17/8100 (0·2%) stool and nasal swabs, respectively. Major genotypes amongst the 306 infection episodes identified were HPeV1 (47·9%), HPeV6 (20·1%), and HPeV3 (18·3%). The incidence rate was 144 episodes/100 child-years (95% CI 128-160). First infections appeared at a median age of 8·0-months (interquartile range 6·0-11·7). Annual seasonal peaks changing from HPeV1 to HPeV3 were observed. Infection was positively associated with age ≥6-months, summer season, non-exclusive breastfeeding at age <3-months, and formal childcare attendance before age 12-months. Sole HPeV infections were either asymptomatic (38·4%) or mild (32·7%), while co-detection with other viruses was common (64·4%). Interpretation: Unlike in hospital-based studies, diverse, dynamically changing HPeV genotypes circulate in the community causing mild or subclinical infections in children. Funding: Australia National Health and Medical Research Council (GNT615700) and Children's Hospital Foundation Queensland (5006). Declaration of Interest: All authors declare no competing interests. Ethical Approval: The Children’s Health Queensland, Royal Brisbane and Women’s Hospital, and The University of Queensland Human Research Ethics Committees approved the study.

Paediatric intensive care admissions during the 2015-2016 Queensland human parechovirus outbreak.

The human parechovirus (HPeV) has emerged as a pathogen causing sepsis-like presentations in young infants, but there is a lack of data on HPeV presentations requiring intensive care support. We aimed to characterise the clinical presentation, disease severity, management and outcome of a population-based cohort of children with microbiologically confirmed HPeV infection requiring admission to paediatric intensive care units (PICUs) in Queensland, Australia during a recent outbreak. This was a multicentre retrospective study of children admitted to PICU between 1 January 2015 and 31 December 2016 with confirmed HPeV infection. Thirty infants (median age 20 days) with HPeV genotype 3 were admitted to PICU, representing 16% of all children with HPeV admitted to hospital and 6.4% of non-elective PICU admissions in children <1 year of age. Children requiring PICU admission were younger than children admitted to hospital (P = 0.001). Apnoea, haemodynamic instability with tachycardia and seizures represented the main reasons for PICU admission. Eleven children (37%) required mechanical ventilation for a median duration of 62 h, 22 (73%) received fluid boluses and 7 (23%) were treated with vasoactive agents for a median duration of 53 h. Median length of stay was 2.62 days. A total of 24 children (80%) fulfilled sepsis criteria, 14 (47%) severe sepsis and 7 (23%) septic shock criteria. Eight (27%) had abnormal brain magnetic resonance imaging. No patient died. We confirm that HPeV infection is an important cause of sepsis-like syndrome in infants with substantial associated morbidity. Optimal management and long-term outcomes require further investigation.

Genetic diversity of human parechoviruses in stool samples, Germany

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.

Encephalitis Related to Human Parechovirus Type 3

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

Polarized Entry of Human Parechoviruses in the Airway Epithelium.

Human parechoviruses (HPeVs), a poorly studied genus within the Picornaviridae family, are classified into 19 genotypes of which HPeV1 and HPeV3 are the most often detected. HPeV1 VP1 C terminus contains an arginine-glycine-aspartic acid (RGD) motif and has been shown to depend on the host cell surface αV integrins (αV ITGs) and heparan sulfate (HS) for entry. HPeV3 lacks this motif and the receptors remain unknown. HPeVs can be detected in patient nasopharyngeal and stool samples, and infection is presumed to occur after respiratory or gastro-intestinal transmission. HPeV pathogenesis is poorly understood as there are no animal models and previous studies have been conducted in immortalized monolayer cell cultures which do not adequately represent the characteristics of human tissues. To bridge this gap, we determined the polarity of infection, replication kinetics, and cell tropism of HPeV1 and HPeV3 in the well-differentiated human airway epithelial (HAE) model. We found the HAE cultures to be permissive for HPeVs. Both HPeV genotypes infected the HAE preferentially from the basolateral surface while the progeny virus was shed toward the apical side. Confocal microscopy revealed the target cell type to be the p63+ basal cells for both viruses, αV ITG and HS blocking had no effect on the replication of either virus, and transcriptional profiling suggested that HPeV3 infection induced stronger immune activation than HPeV1. Genotype-specific host responses may contribute to the differences in pathogenesis and clinical outcomes associated with HPeV1 and HPeV3.

Parechovirus: an important emerging infection in young infants.

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.

Analysis of Human Parechovirus Genotypes in Yokohama District from 2000 to 2016.

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.

Human Parechovirus 1, 3 and 4 Neutralizing Antibodies in Dutch Mothers and Infants and Their Role in Protection Against Disease.

Human parechoviruses (HPeVs) are common pathogens in young children, and in the Netherlands, HPeV1, HPeV3 and HPeV4 are the most frequently detected genotypes. HPeV3 in particular has been associated with severe disease in young infants below 3 months of age while the other genotypes more often infect older children and elicit mild symptoms. We investigated if maternal neutralizing antibodies (nAbs) against HPeV1, HPeV3 and HPeV4 protect young Dutch infants from severe disease related to HPeV infection. We conducted a prospective case-control study of Dutch mother-infant pairs. Thirty-eight HPeV-infected infants and their mothers were included as cases, and 65 HPeV-negative children and their mothers as controls. In control infants, we observed nAb seropositivity rates of 41.4%, 33.3% and 27.6%, with median nAb titers of 1:16, 1:12 and 1:8, against HPeV1, HPeV3 and HPeV4, respectively. In control mothers, nAb seropositivity rates were 84.6%, 55.4% and 60.0% with median nAb titers of 1:128, 1:32 and 1:45 against HPeV1, HPeV3 and HPeV4, respectively. The HPeV3 nAb seroprevalence was significantly lower in HPeV3-infected infants and their mothers (0.0% with P < 0.05 and 10.0% with P < 0.001, respectively). In contrast, no differences in nAb seroprevalence against HPeV1 or HPeV4 could be detected between case and control infants or mothers. Our results suggest that young Dutch infants are protected against severe disease related to HPeV1 and HPeV4 by maternal nAbs, but less so against HPeV3 explaining the distinct age distributions and disease severity profiles of children infected with these HPeV genotypes.

Epidemiology and genetic diversity of human parechoviruses circulating among children hospitalised with acute gastroenteritis in Pune, Western India: a 5-years study.

Human parechoviruses (HPeVs) are known to cause various clinical manifestations including acute gastroenteritis. Although HPeV infections and their genotypes have been detected in human patients worldwide, no such reports are available from India to ascertain the association of HPeVs in acute gastroenteritis. The present study was conducted to determine the clinical features and genetic diversity of HPeVs detected in children hospitalised for acute gastroenteritis. Stool specimens (n = 979) collected from children aged ⩽5 years hospitalised for acute gastroenteritis in Pune, western India during January 2006-December 2010 were included. HPeV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) (5'UTR) followed by genotyping using VP1 gene-based PCR and phylogenetic analysis. HPeV was detected in 13·9% (136/979) of the cases, co-infections with other enteric viruses were found in 43·4%. HPeV was more frequent in children ⩽1 year age with infections reported throughout the year. A total of 102/136 (75%) HPeV strains were genotyped, which comprised 13 different HPeV genotypes. Of these, HPeV1 was the most predominant genotype detected and phylogenetically clustered with the Harris strain which is rarely reported. The study documents circulation of heterogeneous HPeV genotypes. Two variant strains of HPeV4 and 'RGD absent' HPeV5 and 6 strains were also detected. This is the first report of HPeV with diversified genotypes identified in acute gastroenteritis patients from India.

Human Parechovirus Infection in Neonates and Children: An Overview

Pediatricians are becoming increasingly aware of the emergence of human parechovirus (HPeV) following several reports of potentially life-threatening infection in early infancy across the globe from Europe to Australia with episodic seasonal outbreaks. The severity of the HPeV infection varies widely from sporadic mild respiratory or gastrointestinal tract infection in older children to epidemic severe sepsis, myocarditis, and meningoencephalitis in young infants up to 3 months of age. Early complete recovery may sometimes be falsely reassuring, which later can lead to poor neurodevelopmental outcomes. The underlying causative viral agent of meningoencephalitis may remain elusive if a specific laboratory test for HPeV is not requested. Unlike Enterovirus (EV), cerebrospinal fluid (CSF) analysis in HPeV infection may remain misleadingly normal without pleocytosis or abnormal glucose and protein values even in PCR-positive cases. In this review article we attempt to summarize the important clinical information relevant to the practicing pediatricians about HPeV, particularly about its most pathogenic type, HPeV genotype 3 (HPeV3) along with its complications, possible treatment options, and future research direction.