Background. Enteroviruses (EVs) belong to the family Picornaviridae and are a well-known cause of neonatal sepsis and viral meningitis. Human parechoviruses (HPeVs) type 1 and 2, previously named ...echovirus 22 and 23, have been associated with mild gastrointestinal or respiratory symptoms in young children. Six HPeV genotypes are currently known, of which HPeV3 is associated with neonatal sepsis and meningitis. Methods. Cerebrospinal fluid samples from children aged <5 years previously tested by EV-specific polymerase chain reaction (PCR) during 2004–2006 were selected (n=761). Samples from 716 of those children were available for retrospective testing by HPeV-specific real-time PCR. The prevalence of EV and HPeV in these samples was compared. Data on clinical presentation of children infected with HPeV were retrospectively documented. Results. HPeV was found in cerebrospinal fluid samples from 33 (4.6%) of the children. Yearly prevalence of HPeV in cerebrospinal fluid varied remarkably: 8.2% in 2004, 0.4% in 2005, and 5.7% in 2006. EV was detected in 14% (108 of 761 samples), with no variation in yearly prevalence. Children with HPeV in cerebrospinal fluid presented with clinical symptoms of sepsislike illness and meningitis, which led to hospitalization and antibiotic treatment. Conclusion. EV-specific PCRs do not detect HPeVs. The addition of an HPeV-specific PCR has led to a 31% increase in detection of a viral cause of neonatal sepsis or central nervous system symptoms in children aged <5 years. HPeV can be considered to be the second cause of viral sepsis and meningitis in young children, and rapid identification of HPeV by PCR could contribute to shorter duration of both antibiotic use and hospital stay.
Human parechoviruses (HPeVs) are picornaviruses frequently infecting humans. While HPeV1 is associated with mild disease, HPeV3 is the cause of neonatal sepsis and meningitis. To test whether in ...vitro replication kinetics of HPeV1 and HPeV3 could be related to pathogenicity, HPeV1 and HPeV3 strains isolated from patients were cultured on cell lines of gastrointestinal, respiratory and neural origin, and replication kinetics were measured by real-time PCR. No relationship was found between clinical symptoms and in vitro replication of the HPeV1 strains. In contrast, the HPeV3 strains showed faster replication in neural cells and there was a relationship between higher in vitro replication kinetics and neuropathogenicity in the patient. Furthermore, HPeV1 could be neutralized efficiently by its specific antibody and by intravenous immunoglobulins (IVIG), while most HPeV3 strains could not be neutralized. In IVIG, very low neutralizing antibody (nAb) titres against HPeV3 were found. Additionally, very low nAb titres were observed in sera of two HPeV3-infected donors, while high nAb titres against HPeV1 could be detected. Our data suggest that the mild clinical course of HPeV1 infection is primarily influenced by strong nAb responses, while HPeV3 might be difficult to neutralize in vivo and therefore the course of infection will mainly be determined by in vivo cell tropism.
After symptomatic human parechovirus (HPeV) infection in infants, the duration of (mostly asymptomatic) shedding in feces was 2-24 weeks (median 58 days). HPeV cycle threshold value could neither ...differentiate between symptomatic disease and asymptomatic shedding nor between severe and mild disease as high cycle threshold values (indicating low viral loads) were observed in HPeV3-infected children with severe disease.
Polioviruses (PVs) are members of the genus
In the Netherlands, the exclusion of PV circulation is based on clinical enterovirus (EV) surveillance (CEVS) of EV-positive cases and routine ...environmental EV surveillance (EEVS) conducted on sewage samples collected in the region of the Netherlands where vaccination coverage is low due to religious reasons. We compared the EEVS data to those of the CEVS to gain insight into the relevance of EEVS for poliovirus and nonpolio enterovirus surveillance. Following the polio outbreak in Syria, EEVS was performed at the primary refugee center in Ter Apel in the Netherlands, and data were compared to those of CEVS and EEVS. Furthermore, we assessed the feasibility of poliovirus detection by EEVS using measles virus detection in sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV was found in the Ter Apel sewage. We observed significant differences between the three programs regarding which EVs were found. In 6 sewage samples collected during the measles outbreak in 2013, measles virus RNA was detected in regions where measles cases were identified. In conclusion, we detected PVs, nonpolio EVs, and measles virus in sewage and showed that environmental surveillance is useful for poliovirus detection in the Netherlands, where live oral poliovirus vaccine is not used and communities with lower vaccination coverage exist. EEVS led to the detection of EV types not seen in the CEVS, showing that EEVS is complementary to CEVS.
We show that environmental enterovirus surveillance complements clinical enterovirus surveillance for poliovirus detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the presence of adequate surveillance, only a very limited number of Sabin-like poliovirus strains were detected in a 10-year period, and no signs of transmission of oral polio vaccine (OPV) strains were found in a country using exclusively inactivated polio vaccine (IPV). Measles viruses can be detected during an outbreak in sewage samples collected and concentrated following procedures used for environmental enterovirus surveillance.
Background. Non-polio enteroviruses (EVs) and human parechoviruses (PeVs) cause a wide range of human infections. Limited data on their true disease burden exist as standardized European-wide ...surveillance is lacking. Aims. Our aim is to estimate the disease burden of EV and PeV infections in Europe via establishment of standardized surveillance for hand, foot and mouth disease (HFMD) and respiratory and neurological infections caused by these viruses. We will also assess the sensitivity of assays implemented in the network of participating laboratories so that all EV and PeV types are adequately detected. Plan. The European Non-Polio Enterovirus Network (ENPEN) has developed standardized protocols for a prospective, multi-center and cross-sectional hospital-based pilot study. Protocols include guidance for diagnosis, case definition, detection, characterization and reporting of EV and PeV infections associated with HFMD and respiratory and neurological diseases. Over 30 sites from 17 European countries have already registered to this one pilot study, likely to be commenced in 2022. Benefits. This surveillance will allow European-wide comparison of data on EV and PeV infection. These data will also be used to determine the burden of EV and PeV infections, which is needed to guide the further prevention measures and policies.
Wastewater surveillance (WWS) was developed in the early 1960s for the detection of poliovirus (PV) circulation in the population. It has been used to monitor several pathogens, including non-polio ...enteroviruses (NPEVs), which are increasingly recognised as causes of morbidity in children. However, when applying WWS to a new pathogen, it is important to consider the purpose of such a study as well as the suitability of the chosen methodology. With this purpose, the European Non-Polio Enterovirus Network (ENPEN) organised an expert webinar to discuss its history, methods, and applications; its evolution from a culture-based method to molecular detection; and future implementation of next generation sequencing (NGS). The first simulation experiments with PV calculated that a 400 mL sewage sample is sufficient for the detection of viral particles if 1:10,000 people excrete poliovirus in a population of 700,000 people. If the method is applied correctly, several NPEV types are detected. Despite culture-based methods remaining the gold standard for WWS, direct methods followed by molecular-based and sequence-based assays have been developed, not only for enterovirus but for several pathogens. Along with case-based sentinel and/or syndromic surveillance, WWS for NPEV and other pathogens represents an inexpensive, flexible, anonymised, reliable, population-based tool for monitoring outbreaks and the (re)emergence of these virus types/strains within the general population.
Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact ...on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus–infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false–negative variants have been missed.
Human parechoviruses (HPeVs) and enteroviruses (EVs) belong to the family Picornaviridae. EVs are known to cause a wide range of disease such as meningitis, encephalitis, and sepsis. HPeV1 and 2 have ...been associated with mild gastrointestinal or respiratory symptoms in young children. HPeV3 is associated with more severe neonatal infection. Little is known about the epidemiology and pathology of HPeV4-6 in children.
We evaluated the clinical symptoms of the children with an HPeV 4, 5, or 6 infection. The patients with positive HPeV4-6 in stool samples were selected and available plasma or cerebrospinal fluid samples from these patients were tested for HPeV. Data on clinical symptoms, diagnosis, presence and duration of fever, medical history, mean age, use of antibiotics of the children infected with HPeV4-6 were retrospectively documented.
HPeV4-6 were found in 31 of the 277 HPeV positive children (11%). Coinfection with EV was seen in 8 patients. Fever was seen in 13 (42%) patients. Of the HPeV4-6 positive patients, 20 of the 31 children (64%) presented with gastrointestinal complaints and 18 of 31 (58%) patients had respiratory symptoms. The mean age was 14 months, 58% of the patients had an underlying disorder such as bronchomalacia or a cardiac disorder.
Symptomatic HPeV4-6 infections are seen in relative young children and are associated with respiratory and/or gastrointestinal symptoms. HPeV type 4 was detected more frequently than HPeV types 5 and 6.
Enteroviruses (EVs) are highly prevalent viruses worldwide. Recombination is known to occur frequently in EVs belonging to species
,
, and
. Although many recombinant vaccine-derived poliovirus ...(VDPV) strains have been reported, our knowledge on recombination in non-polio EVs in the species
is limited. Here, we combined a dataset consisting of 11 newly generated full-length
sequences and 180 publicly available sequences to study recombination dynamics in non-polio EVs. To identify recombination patterns, maximum likelihood phylogenetic trees of different genomic regions were constructed, and segregation analyses were performed. Recombination was observed between members of the same 3DPol cluster, but was rarely observed between members of different clusters. We hypothesize that this restriction may have arisen through their different compartmentalization in respiratory and enteric tracts related to differences in cellular tropisms so that the opportunity to recombine may not be available.
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