Human parechovirus encephalitis in infants: a retrospective single-center study (2017-2022).

Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA received an increase in reports of PeV infections among infants. A retrospective cohort study describing the clinical characteristics and outcomes of PeV encephalitis in infants aged < 90 days. Rates of PeV encephalitis were determined based on the number of PeV encephalitis cases out of all meningoencephalitis multiplex polymerase chain reaction panel (MEP) obtained among infants aged < 90 days per year. Out of 2115 infants evaluated for meningoencephalitis, 32 (1.5%) cases of PeV encephalitis were identified. All cases had an absence of pleocytosis and normal protein and glucose levels on CSF analysis. Half of the cases presented with a symptomatic triad (fever, rash, and fussiness). More than one-third of cases (39%) presented with a sepsis-like syndrome, 13% presented with seizures, and 25% were admitted to the pediatric intensive care unit (PICU). MRI of the brain was obtained in four of the cases presented with seizure, all of which demonstrated characteristic radiological findings of the periventricular white matter with frontoparietal predominance and involving the corpus callosum, thalami, and internal and external capsules. Rates of PeV encephalitis varied from year to year, with the highest rates in 2018 and 2022. PeV was the second most detected pathogen in MEP in both 2018 and 2022, and the fifth most detected pathogen in all positive MEP during the study period 2017-2022. CONCLUSION: PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks. WHAT IS KNOWN: • PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days. • Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization.. • Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years.. WHAT IS NEW: • Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis. • Knowledge of the biennial seasonality pattern in PeV infection. • PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.

Identification and genome characterization of novel parechovirus sequences from Hipposideros armiger in China.

BACKGROUND: Bats were identified as a natural reservoir of emerging and re-emerging infectious pathogens threatening human health and life. METHODS: This study collected 21 fecal samples of Hipposideros armiger in Mengla County of Xishuangbanna Prefecture Yunnan Province to combine one pool for viral metagenomic sequencing. RESULTS: Two nearly complete genomes of parechoviruses, BPeV11 and BPeV20, were sequenced. Genome analysis revealed that BPeV11 and BPeV20 follow a 3-3-4 genome layout: 5' UTR-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The prevalence of BPev11 and BPev20 by Nested-PCR showed that 1 of 21 fecal samples was positive. Based on amino acid identity comparison and phylogenetic analysis of P1, 2C, and 3D, BPeV11 and BPeV20 were closely related to but distinct from FPeVs. CONCLUSION: It was probably proposed to be a novel species in the genus Parechovirus of the family Picornaviridae. The isolation of BPev11 and BPev20 from H. armiger in China is the first complete genome of parechovirus isolations from bat feces of the genus Hipposideros.

Development of a real-time RT-PCR assay for the detection of pan-human parechoviruses.

BACKGROUND: Parechoviruses (PeV-As), which constitute a new genus within the family Picornaviridae, have been associated with numerous localized outbreaks of serious diseases, such as coryza, pneumonia, maculopapular exanthem, and conjunctivitis. However, to the best of our knowledge, only a few laboratories worldwide conduct tests for the identification of this group of viruses. Therefore, in this study, we aimed to develop and validate a real-time RT-PCR assay for the identification of PeV-As. METHODS: To design and validate a real-time PCR primer-probe targeting the 5'-UTR region of PeV-As, the 5'-UTR sequences of PeV-As available in GenBank were aligned using the MUSCLE algorithm in MEGA v7.0. Thereafter, the highly conserved 5'-UTR region was selected, and its primer-probe sequence was designed using Primer Premier v5.0. This primer-probe sequence was then evaluated for specificity, sensitivity, and repeatability, and for its validation, it was tested using fecal samples from 728 healthy children living in Beijing (China). RESULTS: The PeV-A real-time RT-PCR assay detected only the RNA-positive standards of PeV-A genotypes (1-8, 14, 17, and 18), whereas 72 serotypes of non-PeV-A EV viruses were undetected. In addition, the VP1 region of these 11 PeV-A genotypes that tested positive were amplified using the primers designed in this study. Typing results indicated that eight, one, and two strains of the 11 were PeV-A1, PeV-A4, and PeV-A6, respectively. We also determined and presented the genetic characterization and phylogenetic analyses results corresponding to these 11 VP1 region sequences. Furthermore, real-time RT-PCR assay showed good sensitivity with LOD of 102 copies/µL. Positive results in eight parallel experiments at each concentration gradient from 107 copies/µL to 102 copies/µL, indicating good repeatability. CONCLUSION: Our findings suggested that the real-time RT-PCR assay developed in this study can be applied for routine PeV-A identification. We detected PeV-A1, 4 and 6 genotypes in the 728 faecal samples using this method. Additionally, we believe that our results will serve as a foundation for further studies on PeV-As and facilitate the expansion of the gene sequence information available in GenBank.

Detection and Characterization of Human Enteroviruses, Human Cosaviruses, and a New Human Parechovirus Type in Healthy Individuals in Osun State, Nigeria, 2016/2017.

Human enteroviruses and human parechoviruses are associated with a broad range of diseases and even severe and fatal conditions. For human cosaviruses, the etiological role is yet unknown. Little is known about the circulation of non-polio enteroviruses, human parechoviruses, and human cosaviruses in Nigeria. A total of 113 stool samples were collected from healthy individuals in Osun State between February 2016 and May 2017. RT-PCR assays targeting the 5' non-coding region (5' -NCR) were used to screen for human enteroviruses, human parechoviruses, and human cosaviruses. For human enteroviruses, species-specific RT-PCR assays targeting the VP1 regions were used for molecular typing. Inoculation was carried out on RD-A, CaCo-2, HEp-2C, and L20B cell lines to compare molecular and virological assays. Ten samples tested positive for enterovirus RNA with 11 strains detected, including CV-A13 (n = 3), E-18 (n = 2), CV-A20 (n = 1), CV-A24 (n = 1), EV-C99 (n = 1), and EV-C116 (n = 2). Three samples tested positive for human parechovirus RNA, and full genome sequencing on two samples allowed assignment to a new Parechovirus A type (HPeV-19). Thirty-three samples tested positive for cosavirus with assignment to species Cosavirus D and Cosavirus A based on the 5'-NCR region. Screening of stool samples collected from healthy individuals in Nigeria in 2016 and 2017 revealed a high diversity of circulating human enteroviruses, human parechoviruses, and human cosaviruses. Molecular assays for genotyping showed substantial benefits compared with those of cell-culture assays.

A 5-year study of human parechoviruses in children living in bad sanitation conditions and non-polio acute flaccid paralysis children from Greece.

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.

Neonatal nonpolio enterovirus and parechovirus infections.

Nonpolio enteroviruses and parechoviruses are frequent causes of neonatal infection. Clinical manifestations of infection range from asymptomatic infection to mild infection without sequelae to septic shock with muiltiorgan failure. Neonates with clinically apparent infection typically have mothers and/or other contacts with recent symptoms consistent with a viral illness. Severe neonatal infection with nonpolio enterovirus or parechovirus cannot be differentiated clinically from serious bacterial infection. The preferred method for diagnosing neonatal nonpolio enterovirus or parechovirus infection is PCR as it is rapid, sensitive, specific, and commercially available for the detection of virus from various clinical specimens. Investigational agents such as the capsid inhibitors pleconaril and pocapavir show promise for treatment of neonatal enterovirus infections, and other investigational agents are being developed. This review focuses on the epidemiology, diagnosis, and treatment of neonatal nonpolio enterovirus and parechovirus infections.

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.

Nosocomial Outbreak of Parechovirus 3 Infection among Newborns, Austria, 2014.

In 2014, sepsis-like illness affected 9 full-term newborns in 1 hospital in Austria. Although results of initial microbiological testing were negative, electron microscopy identified picornavirus. Archived serum samples and feces obtained after discharge were positive by PCR for human parechovirus 3. This infection should be included in differential diagnoses of sepsis-like illness in newborns.

Detection and characterization of enteroviruses and parechoviruses in healthy people living in the South of Côte d'Ivoire.

BACKGROUND: Human enteroviruses (EVs) and parechoviruses (HPeVs) belong to the family Picornaviridae. Although most EV and HPeV infections remain asymptomatic, both pathogens can cause a wide spectrum of clinical manifestations ranging from respiratory or gastrointestinal symptoms to myocarditis, neonatal sepsis, and infections of the central nervous system. OBJECTIVES: Aim of the present study was to investigate the spectrum of EVs and HPeVs in apparently healthy adults and children living in the South of Côte d'Ivoire. STUDY DESIGN: The study included 105 stool samples obtained from healthy individuals aged 0-53 years between June 2013 and December 2014 in the Sud-Como region of Côte d'Ivoire. After collection and shipment to Germany, the samples were analyzed by real-time PCR for the presence of EVs and HPeVs RNA. Molecular typing and virus isolation of all samples were performed.''é RESULTS: Out of 105 samples, 24 (22.8%) were EV positive and six (5.2%) were HPeV positive. Twenty-one EV positive samples could be characterized with serotypes belonging to EV group A-C, while three could not be further specified. Interestingly, several rarely described serotypes were identified, e.g., EV-C99, EV-B93, EV-C116, and EV-A119. Typing of HPeV positive samples resulted in HPeV-1 and -5 detections, while one isolate could not be assigned to the known HPeV types. CONCLUSIONS: This study showed a large variety of EV strains in healthy people in the South of Côte d'Ivoire and provided the first available data about HPeV infections in a sub-Saharan African country.

Pediatric parechovirus infections.

Human parechoviruses (HPeVs) are members of the large and growing family of Picornaviridae. Although 16 types have been described on the basis of the phylogenetic analyses of the VP1 encoding region, the majority of published reports relate to the HPeV types 1-8. In pediatrics, HPeV1, HPeV2 and HPeV4-8 mainly cause mild gastrointestinal or respiratory illness; only occasionally more serious diseases have been reported, including myocarditis, encephalitis, pneumonia, meningitis, flaccid paralysis, Reye syndrome and fatal neonatal infection. In contrast, HPeV3 causes severe illness in young infants, including sepsis and conditions involving the central nervous system. Currently, the most sensitive method for detecting HPeV is real-time polymerase chain reaction assays on stools, respiratory swabs, blood and cerebrospinal fluid. However, although it is known that HPeVs play a significant role in various severe pediatric infectious diseases, diagnostic assays are not routinely available in clinical practice and the involvement of HPeV is therefore substantially underestimated. Despite long-term efforts, the development of antiviral therapy against HPeVs is limited; no antiviral medication is available and the use of monoclonal antibodies is still being evaluated. More research is therefore needed to clarify the specific characteristics of this relevant group of viruses and to develop appropriate treatment strategies.

[Human parechovirus-3 infection in a neonate with fever and suspected sepsis]. / Infección por parechovirus 3 en un neonato con fiebre y sospecha de sepsis.

The human parechovirus (HPeV) are viruses of the recently described Picornaviridae family and are causing several infections in young children. The pathology associated with these viruses is beginning to emerge. The HPeV type 3, has been described particularly in association with sepsis-like febrile syndromes, meningitis and encephalitis in very young infants and neonates. We report the case of a 14-day-old girl with a fever and clinical sepsis that required hospitalization and in which HPeV-3 was identified in the cerebrospinal fluid. The blood, urine and cerebrospinal fluid bacterial cultures were negative, and the patient improved. This case illustrates the usefulness of investigating parechovirus infection in neonates with fever or suspected sepsis.