Human parechovirus (PeV) is an increasingly recognized cause of meningoencephalitis (ME) in infants. The US 2022 outbreak provided opportunity to analyze the clinical presentation and predictors of severe disease in affected infants. We conducted a multicenter retrospective review of infants diagnosed with PeV ME during the outbreak. We examined demographics, clinical features, laboratory findings, and neuroimaging results. Logistic regression was used to identify predictors of complicated disease and abnormal brain magnetic resonance imaging (MRI). Complicated disease was defined as requiring intensive care or findings of an abnormal brain MRI or electroencephalogram. 139 infants had PeV ME. The median age was 19days. Fever was the most common presenting symptom (89.2%) and was associated with uncomplicated disease and normal MRI. A total of 42 (30.2%) infants had complicated disease. Hypothermia (36.5% vs 5.1%), somnolence (38.1% vs 13.4%), poor feeding (76.1% vs 47.4%), hemodynamic instability (28.5% vs 3%), seizures (57.1% vs 4.1%), apnea (40.4% vs 0%), hypoglycemia (16.6% vs 1%), mechanical ventilation (23.8% vs 0%), and inotropic support (11.9% vs 0%) were associated with complicated disease. Younger age and seizures were predictors of abnormal MRI on multivariable analysis (adjusted odds ratio, 0.92 [0.48-0.99] and 40.1 [3.49-460.7], respectively). Laboratory findings, including cerebrospinal fluid indices, were rarely abnormal. Despite nonspecific symptoms on presentation and normal laboratory values, PeV can cause complicated disease, requiring clinicians to maintain high suspicion for this infection. We suggest PeV evaluation in workup of infant sepsis cases, neuroimaging in patients at high risk, and long-term developmental follow-up.

Objective. To assess the detection frequency of rare (minor) enteric viruses in patients with acute gastroenteritis in the capital region of the Republic of Belarus, and to study the prevalence of them in general population based on wastewater analysis, with the subsequent establishment of their genotypes.Materials and methods. Acute gastroenteritis (AGE) of viral etiology is caused by a wide range of different viruses, the prevalence of individual types of which varies significantly in different countries. 235 fecal samples of acute gastroenteritis (AGE) patients and 233 wastewater samples were analyzed during 2022. Detection of rotaviruses (RV), noroviruses of genogroups 1 and 2 (NoV 1 and 2), adenoviruses F (AdV), enteroviruses (EV), astroviruses (AsV), sapoviruses (SpV), parechoviruses (PEV), bocaviruses (BoV) and aichi viruses (AiV) was performed with “real time” multiplex PCR. Genotypes of BoV, AsV, SpV were determined by use of type-specific PCR and sequencing.Results. It was found that RV (61.3%), NoV2 (14.5%) and AdV (12.8%) were predominant in patients with AGE, and minor viruses were detected in a total of 6.4% of patients. AdV (33.6%), BoV (31.4%), RV (11.7%) and AsV (6.7%) were most frequently detected in wastewater. Molecular genetic typing of BoV, AsV, SpV made it possible to determine the circulation of the following genotypes: BoV genotypes HBoV-1, HBoV-2, HBoV-3, AsV genotype HAsV-1 and SpV genotype HuSpV GI.2.Conclusion. The obtained results indicate that, despite the low frequency of detection of BoV and AsV in patients with a clinical diagnosis of AGE, they widely circulate in the population and may be the cause of AGE mild cases that have not seen by infectologists and for which laboratory diagnostics have not been carried out.

Abstract Background Enteroviruses (EV)—a group of viruses including echoviruses (E) and coxsackieviruses (CV)—and parechoviruses (PeV) can cause a range of symptoms, including respiratory illness; hand, foot, and mouth disease; acute flaccid myelitis; meningitis; and sepsis. Neonates (persons < 1 month old) are at higher risk of severe EV or PeV disease. We analyzed data from the National Enterovirus Surveillance System (NESS) to assess types and outcomes of neonatal EV and PeV infections reported during 2004–2022. Methods NESS is a passive, laboratory-based surveillance system that collects reports of positive EV and PeV virus type results in the United States. We analyzed data on EV and PeV specimens collected during January 1, 2004–December 31, 2022. Outcome data (defined as whether the patient died) were reported to NESS during 2014–2022. Chi-squared tests were used to compare virus type frequencies by age, with differences considered significant if p < 0.05. Results Overall, 10,833 EV and PeV infections were reported during 2004–2022: 9,197 (85%) had reported age, of which 753 (8%) were among neonates. Among 631 neonatal EV or PeV infections with identified virus type (84%), Coxsackievirus type B5 (CVB5) (76; 12%), CVB3 (64; 10%), PeVA3 (61; 10%), E11 (54; 9%), and CVB4 (52; 8%) were detected most frequently. Compared with persons ≥ 1 month old, CVB types 1–5, PeVA3, and E11 were significantly more likely to be detected among neonates, whereas EV-D68 and E30 infections were less common. Among 483 neonates with EV or PeV infections during 2014–2022, 68 (14%) had known outcome, of whom 16 (24%) died. Conclusion EV and PeV infections can cause severe disease among neonates. The frequencies of EV and PeV virus types detected among neonates differ from those among persons ≥1 month old, although this may partially reflect testing differences by age. Assessing mortality among neonates with EV and PeV illness is limited by incomplete outcome data and lack of systematic EV and PeV testing and reporting, which may be biased toward including patients with more severe illness. Strengthening capacity for EV and PeV testing, typing, and surveillance would be beneficial for understanding the disease burden among neonates and informing treatment options and prevention measures. Disclosures All Authors: No reported disclosures

Although influenza viruses cause only one-fifth of severe acute respiratory infections (SARI) in Burkina Faso, the other viral causes of SARI remain poorly investigated to inform clinical and preventive decision making. Between 2016 and 2019, we prospectively enrolled inpatients meeting the World Health Organization (WHO) case definition of SARI in Burkina Faso. Results of viral etiologies among inpatients tested negative for influenza using the Fast Track Diagnostics Respiratory Kits (FTD-33) were reported. Of 1541 specimens tested, at least one respiratory virus was detected in 76.1% of the 1231 specimens negative for influenza virus. Human rhinoviruses (hRVs) were the most detected pathogens (476; 38.7%), followed by human adenoviruses (hAdV) (17.1%, 210/1231), human respiratory syncytial virus (hRSV) (15.4%, 189/1231), enterovirus (EnV) (11.2%, 138/1231), human bocavirus (hBoV) (7.9%, 97/1231), parainfluenza 3 (hPIV3) (6.1%, 75/1231), human metapneumovirus (hMPV) (6.0%,74/1321), parainfluenza 4 (hPIV4) (4.1%, 51/1231), human coronavirus OC43 (hCoV-OC43) (3.4%, 42/1231), human coronavirus HKU1(hCoV-HKU1) (2.7%, 33/1231), human coronavirus NL63 (hCoV-NL63) (2.5%, 31/1231), parainfluenza 1 (hPIV1) (2.0%, 25/1231), parainfluenza 2 (hPIV2) (1.8%, 22/1231), human parechovirus (PeV) (1.1%, 14/1231), and human coronavirus 229E (hCoV-229E) (0.9%, 11/1231). Among SARI cases, infants aged 1-4 years were mostly affected (50.7%; 622/1231), followed by those <1 year of age (35.7%; 438/1231). Most detected pathogens had year-long circulation patterns, with seasonal peaks mainly observed during the cold and dry seasons. Several non-influenza viruses are cause of SARI in Burkina Faso. The integration of the most common pathogens into the routine influenza surveillance system might be beneficial.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Ourreport demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Unveiling indicator, enteric, and respiratory viruses in aircraft lavatory wastewater using adsorption-extraction and Nanotrap® Microbiome A Particles workflows

To define the presentation, spectrum of illness, and outcomes in infants with parechovirus (PeV) meningitis admitted to our inpatient general pediatrics service during a spike in incidence of admissions in summer 2022. This study is a retrospective case series of all patients aged 3 months and younger discharged from our institution with a CSF BioFire (BioFire Diagnostics, Salt Lake City, UT) FilmArray Polymerase Chain Reaction Meningitis/Encephalitis Panel result positive for PeV between January 1 and September 19, 2022. We collected and analyzed clinical and demographic data. Eighteen infants with PeV meningitis were admitted within our time frame, with 8 (44%) of the admissions occurring in July. Patients' mean age was 28.7 days and mean length of stay was 50.5 hours. Although all had a history of fever, only 72% were febrile on presentation. Laboratory findings showed a procalcitonin of less than 0.5 ng/mL in 86% of the 14 patients who had it drawn and no cerebrospinal fluid (CSF) pleocytosis in 83% of the patients who had CSF cell counts sent. Neutropenia was present in 17%. Although 89% of infants were given initial antibiotics, antibiotics were discontinued in 63% once their CSF panel returned positive for PeV, and in all by 48 hours. Infants hospitalized with PeV meningitis were febrile and fussy, but experienced uncomplicated hospital stays without neurological deficits. Parechovirus meningitis must be considered as a common cause of acute viral meningitis in young infants even without CSF pleocytosis. This study, although limited in scope and follow-up, can potentially assist in the diagnosis and treatment of PeV meningitis at other institutions.

Disruption of seasonal enterovirus and parechovirus detections in the CSF and plasma of children during the COVID-19 pandemic.

In early spring 2022, clinical microbiologists in Tennessee noticed an increasing trend of parechovirus (PeV) central nervous system (CNS) infections in infants <3 months through routine monitoring of test results for quality assurance. This initiated a discussion on ClinMicroNet, an online forum for clinical microbiologists supported by the American Society of Microbiology (ASM), about the unseasonably early circulation of PeV and increased CNS infections. Additional microbiologists in the United States noted similar trends, though reports differed by geographic region. The Tennessee trend was reported to the Tennessee Department of Health and then to the Centers for Disease Control and Prevention (CDC). These and other observations prompted release of a CDC Health Alert Network Health Advisory on July 12, 2022, which warned of increased PeV-A3 circulation in the United States. The CDC Health Advisory recommended inclusion of PeV in the differential for patients, particularly infants, with meningoencephalitis during seasons of high transmission (summer and fall). Notably, the presentation of meningoencephalitis in the Tennessee cases differed from conventional presentations in that cerebrospinal fluid pleocytosis was absent in most of the children. A case series of the Tennessee patients was thereafter reported in the CDC Morbidity and Mortality Weekly Report (MMWR), detailing 23 PeV CNS infections detected with a US Food and Drug Administration-approved multiplex molecular panel in infants <3 months over 6 weeks (1).

Occurrence of multiple respiratory viruses in wastewater in Queensland, Australia: Potential for community disease surveillance

Background and Objective: Acute Encephalitis Syndrome (AES) leads to significant mortality and morbidity in children. This study was undertaken to identify the viral causes of AES and its correlation with clinicodemographic profile. Methods: This cross-sectional study included 100 children aged 1 to 12 years presenting with fever of &lt;14 days duration and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) [1]. Cerebrospinal Fluid (CSF) was collected aseptically by lumbar puncture for biochemical and cytological analysis, and for bacteriological culture. Multiplex PCR for the viruses HSV1, HSV2, Varicella zoster virus, Enterovirus, Mumps and Parecho virus was carried out. Serology for Japanese Encephalitis (JE) was done in blood and CSF by ELISA method. Dengue NS1 antigen and IgM ELISA was carried out in both blood and CSF samples. Serum IgM antibody for scrub typhus was done by ELISA method. Results: Out of 100 children viral cause was detected in 21 patients (Japanese encephalitis -16, Dengue – 4, Varicella zoster virus, Enterovirus and Mumps virus – 1 each). Serum IgM ELISA for scrub typhus was positive in 6 patients. Multiple viral etiology was seen in 2 patients. Mortality was significantly more in females (p=0.021), GCS &lt;8 (p &lt;0.001). Mortality was significantly more with higher CSF neutrophils and higher proteins (p&lt;0.05). Interpretation and Conclusion: This study concludes that viral causes specially JE contributed in AES in North India. Hence viral pathogens including JE needs to be considered as one of major causative agents while treating patients of AES and further emphasis has to be given for JE vaccination in this region.

Enterovirus meningitis in Mayotte French Comoros Island, March-June 2019.

These results suggest that the impact of PeV-A3-CNS infection on gross motor neurodevelopment in young children might manifest later in life. They highlight the importance of longitudinal neurodevelopmental assessments of children with PeV-A3-CNS infection up to school age. •Human parechovirus (PeV) is a major cause of central nervous system infection (CNS infection) in newborns and infants. •There is interest in the neurological and neurodevelopmental outcome of newborns and infants with PeV-A3-CNS infection. •This prospective study compares the motor neurodevelopment of term-born newborns and infants with PeV-A3-CNS infection with those with EV-CNS infection and with norm references. •The results support the importance of follow-up of newborns and infants with PeV-A3-CNS infection to detect subtle neurodevelopmental delay and start early interventions.

Human parecho viruses are small, non-enveloped, single stranded RNA viruses within parechovirus genus of the large picornaviridae family. In new-born it can cause gastroenteritis, sepsis and encephalitis. We report case series of parecho-virus encephalitis admitted to a tertiary care centre, Perinthalmanna. Parechoviral encephalitis is an endemic disease seasonally present (May-July) in certain regions of Northern part of Kerala. HPeV are viruses that cause CNS infection in the neonatal period, resulting in white matter lesions that can be visualised with MRI. In a retrospective study, 4 newborn babies of neonatal HPeV encephalitis diagnosed on the basis of clinical and radiological findings with a seasonality were assessed. HPeV encephalitis needs to be in differential diagnosis when neonates and young infants present with seizure and sepsis. HPeV infection must be considered in infants with specific pattern of white matter change but no convincing history of a perinatal hypoxic-ischaemic insult.

Background: Little is known about the etiology of meningitis in the MENA region, including Qatar. Viral agents are considered the major cause for meningitis worldwide. Here, we present primary data about the etiology and clinical and demographic characteristics of viral meningitis (VM) in Qatar between 2015 and 2018.Methods: We retrospectively collected data from Hamad Medical Corporation (HMC), which provides about 80% of healthcare services in Qatar. Data were collected for the period between 2015 and 2018. During this time period, 6,705 specimens were collected from patients with suspected meningitis attending HMC and primary healthcare centers. These specimens were tested for a panel of viruses using the “FTD Viral meningitis” multiplex real-time PCR kit that detects Adenovirus (ADV), Human herpesvirus 1&2 (HSV1 and HSV2), Epstein–Barr virus (EBV), Enteroviruses (EV), Cytomegalovirus (CMV), Varicella zoster virus (VZV), and Parechovirus (PV).Results: Only 10.9% (732/6,705) of all suspected meningitis cases were caused by viral agents. 60.9% of the reported cases were males, compared to 39.1% in females. Most of the infections (73.9%) were reported in children younger than 10 years of age. EV were identified as the main causative agent (68.7%), followed by EBV (7.5%) and ADV (6.8%). Other viral agents including VZV, PV, HSV-1, and HSV-2 were also detected with a lower frequency. Confirmed VM were more prevalent among Qatari subjects compared to other nationalities. We observed no specific seasonality of viral agents, but a slight rise was recorded during the spring seasons (March to June). Fever (59.4%, 435/732) and acute central nervous system (CNS) infection (15.6%, 114/732) were initial symptoms of most cases.Conclusion: This is the first report about the molecular epidemiology of VM in Qatar. In line with the international records, our data showed that EV is responsible for 68.7% of Qatar's VM cases. Further studies are needed to genotype and serotype the identified viruses.

Non-polio enteroviruses (NPEV) and parechoviruses (PeV) are widespread pathogens that cause significant morbidity. Surveillance is based on culturing or genotyping of virus strains found in clinical samples. Sero-surveillance, by measuring neutralising antibodies (nAb) through virus neutralisation assays (VNA), could provide additional information as it offers a more comprehensive overview of exposure to circulating types in the general population. In our study we evaluated Intravenous immunoglobulins (IVIG) to generate sero-surveillance data. We performed VNA of nineteen NPEV and PeV with Dutch IVIG batches from two different time points (2010 and 2017) and an IVIG batch from Vietnam (2011). We compared our findings with geno- and sero-surveillance data and evaluated changes over time and between the two countries. Our findings show a good correlation with what is known from geno-surveillance data. The highest nAb titres were found against strains from Enterovirus B, while we did not observe nAb titres against strains belonging to Enterovirus C. In conclusion, we demonstrated that sero-surveillance by means of IVIG can be used to obtain insight into circulation of EV and PeV genotypes. This is of particular interest for public health, to evaluate changes over time and population susceptibility to emerging genotypes.

Enterovirus (EV) and parechovirus (PeV) are leading viral causes of central nervous system (CNS) infection among hospitalized neonates and young infants, yet testing for PeV is not routinely performed. The goal of our study was to determine how EV and PeV CSF RT-PCR testing impacted the duration of antibiotic use and the length of hospitalization (LOS) in children ≤6 months old with suspected CNS infection. This retrospective cohort study at Children's Mercy Kansas City evaluated data from patients ≤6 months old for whom routine CSF EV and PeV reverse transcription-PCR (RT-PCR) testing was performed during January 2011 to December 2018. Electronic data were abstracted from the electronic medical record, including demographics, systemic antimicrobial use, imaging data, herpes simplex virus (HSV) testing, and overall hospital charges. Among 1,926 patients, 345 (17.9%) were RT-PCR positive for EV and 172 (8.9%) were positive for PeV. A significantly shorter LOS was observed for patients with EV (51.6 h; P < 0.001) and PeV (66.3 h; P = 0.048) compared to patients that tested negative for both viruses (74.1 h). Discontinuation of empirical antibiotic therapy following test result availability occurred more frequently for PeV patients (57.8%; P = 0.03) and EV patients (65.4%; P < 0.001) than RT-PCR-negative patients (48.5%). Routine EV/PeV RT-PCR testing of cerebrospinal fluid (CSF) samples in children impacted care of hospitalized neonates and young infants. Rapid and prompt diagnosis has the potential to reduce antibiotic usage, length of stay, and patient charges.

BackgroundEnterovirus (EV) and human Parechovirus (PeV) cause a range of illness including asymptomatic to systemic infections. The host immune response in children, especially the one induced by PeV, is largely unknown. The aim of this study was to determine the immune response induced by EV and PeV in cerebrospinal fluid (CSF) and plasma obtained from children with systemic infection.MethodsLeft-over CSF and paired blood samples collected from children with laboratory confirmed EV and PeV central nervous system-infection were enrolled in this study. EV/PeV-negative CSF and paired plasma from children was used as controls. Level of cytokines and chemokines were measured using a customized 21-plex ELISA panel that included 16 cytokines and 5 chemokines (Millipore, CA). Additionally, clinical characteristics of all the patients were collected to determine the potential association between the immune response and pathogenicity.ResultsTotal of 74 samples were enrolled and divided into 3 groups, EV (n = 27), PeV (n = 23) and control group (n = 24). Median age of all the three groups was 2 weeks (IQR 2–4 weeks).The key analytes which had a significant difference between each groups are show in the Table. In general, EV induced more robust cytokine secretion than PeV and control group. Anti-viral response such as IFN-g was remarkably absent in both CSF and plasma in PeV group compared with EV group (P < 0.05). Only IL-8 was significantly higher (P < 0.05) in EV CSF group compared with any other groups or sample types. Level of all the chemokines measured were much higher in all the three groups but significant difference was found between PeV CSF and plasma for IP-10 and MCP-1 chemokines (P < 0.05).ConclusionIn this study, we demonstrate that EV and PeV induces distinct immune response in children with systemic infections. While EV induces more robust inflammation, PeV-induced inflammation appears to be either weak or absent in CSF, but robust in plasma. The suppressed pro-inflammatory response might facilitate PeV growth and proliferation in CSF and might play a role in disease severity. Further studies are needed to fully understand the differential immune response induced by these two viruses.DisclosuresAll authors: No reported disclosures.

Prospective research of human parechovirus and cytokines in cerebrospinal fluid of young children less than one year with sepsis-like illness: Comparison with enterovirus

BackgroundHospital-based studies identify parechovirus (PeV), primarily PeV-A3, as an important cause of severe infections in young children. However, few community-based studies have been published and the true PeV infection burden is unknown. We investigated PeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study. MethodsAustralian 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 PeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus codetections were investigated. ResultsPeV was detected in 1423 of 11 124 (12.8%) and 17 of 8100 (0.2%) stool and nasal swabs, respectively. Major genotypes among the 306 infection episodes identified were PeV-A1 (47.9%), PeV-A6 (20.1%), and PeV-A3 (18.3%). The incidence rate was 144 episodes (95% confidence interval, 128–160) per 100 child-years. First infections appeared at a median age of 8 (interquartile range, 6.0–11.7) months. Annual seasonal peaks changing from PeV-A1 to PeV-A3 were observed. Infection was positively associated with age ≥6 months, summer season, nonexclusive breastfeeding at age <3 months, and formal childcare attendance before age 12 months. Sole PeV infections were either asymptomatic (38.4%) or mild (32.7%), while codetection with other viruses in stool swabs was common (64.4%).ConclusionsIn contrast with hospital-based studies, this study showed that diverse and dynamically changing PeV genotypes circulate in the community causing mild or subclinical infections in children.Parechovirus can cause severe illnesses in children. However, studies focus mainly on hospitalized populations. True disease burden in the community remains largely unknown. From our community-based cohort, we found diverse parechovirus genotypes in the community, causing mild or subclinical infections in children.