Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND: 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. OBJECTIVES: To determine PCR detection rates for HPeV-3 and EVs in serum and cerebrospinal fluid (CSF) samples from febrile neonates and young infants. STUDY DESIGN: This prospective study identified viruses in serum and CSF samples collected from febrile neonates and young infants (age <4 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. RESULTS: 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. CONCLUSIONS: 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.

DOI： 10.1016/j.jcv.2021.104736

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND: Enterovirus D68 (EV-D68) causes asthma-like respiratory infection in children. Several EV-D68 outbreaks have been reported worldwide since the largest outbreak occurred in the United States in 2014. We experienced an accumulation of pediatric cases with asthma-like respiratory illness in Niigata, Japan, in 2018. STUDY DESIGN: To determine whether EV-D68 was responsible for the case accumulation, this prospective observational study evaluated children hospitalized in 1 of 8 hospitals with asthma-like respiratory illness in Niigata, Japan, during October and November 2018. Diagnoses were made by EV-D68-specific RT-PCR using nasopharyngeal samples. The clade was identified by sequence analyses, and a phylogenetic tree was created. To evaluate seasonal variation, data from pediatric cases with asthma-like respiratory illness in 2018 were retrospectively analyzed. RESULTS: In 2018, 114 children were hospitalized with asthma-like respiratory illness in October and November, and 47 nasopharyngeal samples were collected. EV-D68 was detected in 22/47 (47%) patients during the study period. The phylogenetic tree revealed that all strains belonged to the clade B3 branch, which has been detected worldwide every 2 years since 2014. CONCLUSIONS: EV-D68 was the associated pathogen for asthma-like respiratory illness in children in Japan in 2018. Clade B3, the dominant clade in outbreaks worldwide, was responsible for the outbreak. Detection and detailed virologic analysis of EV-D68 is important as part of worldwide surveillance, as it will aid in understanding the epidemiologic characteristics of EV-D68 infection.

DOI： 10.1097/inf.0000000000002889

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Parechovirus-A3 (PeV-A3) and the enteroviruses (EVs) are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants; however, differences in the clinical presentations of two infections are not well described. OBJECTIVES: To describe the clinical presentations of PeV-A3- and EVs-related diseases and develop a novel scoring system to differentiate two diseases. STUDY DESIGN: This prospective study used real-time PCR and genetic sequencing to evaluate viral etiologies of febrile neonates and infants <4 months with suspected sepsis or meningoencephalitis in Niigata area, Japan, in 2014-2016. The clinical manifestations of PeV-A3- and EVs-infected patients were compared, and a novel scoring system was developed after identifying the most distinguishable clinical findings, followed by the external cohort validation. RESULTS: In 210 patients evaluated, we identified 56 PeV-A3-infected (27%) and 43 EVs-infected (20%) patients. The following clinical manifestations were significant in PeV-A3-infected patients, as compared with EVs-infected patients; a higher body temperature (38.9°C vs. 38.5°C, P < .01) and heart rate (181/min vs. 168/min, P = .01), cold extremities (72% vs. 34%, P < .01) and skin mottling (65% vs. 23%, P < .01), lower white blood cell count (5,200/μL vs. 8,900/μL, P < .01) and incidence of cerebrospinal fluid (CSF) pleocytosis (2% vs. 63%, P < .01). Using some of these significant findings, the scoring system successfully distinguished the diseases (accuracy: 86% and 83% for the derivative and external validation cohorts, respectively). CONCLUSIONS: We found significant clinical manifestations in PeV-A3-infected patients compared to EVs-infected patients. The scoring system may be helpful to distinguish two infections, especially at onset of outbreak.

DOI： 10.1016/j.jcv.2019.104256

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press  

BACKGROUND: Parechovirus A (PeV-A) is an important cause of sepsis and meningoencephalitis in neonates and young infants. Thus, identifying the source of PeV-A is essential for prevention; however, little is known regarding the spread of PeV-A among family members of PeV-A-infected neonates and young infants. METHODS: In this prospective study, we evaluated stool samples from family members of PeV-A-infected neonates and infants younger than 4 months who presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016. Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated during this period. Real-time polymerase chain reaction followed by sequence analysis was used for viral diagnosis using serum and/or cerebrospinal fluid samples. RESULTS: Among 54 febrile patients, the stool samples of 14 (26%) and 12 (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from 54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were available. The rate of PeV-A positivity in these samples was higher among the children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of 13) of the adults were asymptomatic. Similarly, among 53 stool samples from family members (31 adults and 22 children) of 11 EV-infected patients, the rate of EV positivity in the stool samples was higher among the children (91% [20 of 22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were 45% (9 of 20) among the children and 85% (11 of 13) among the adults in family members with EV-positive stool. CONCLUSIONS: Similar to EVs, PeV-A was detected frequently in stool samples from family members of PeV-A-infected patients. Among family members with PeV-A-positive stool, adults were more likely than children to be asymptomatic and therefore could be an important source of PeV-A infection.

DOI： 10.1093/jpids/piy079

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Language：English   Publishing type：Research paper (scientific journal)  

This 3-year follow-up study evaluated neutralizing antibody titers (NATs) against parechovirus-A3 (PeV-A3) in neonates and young infants who developed PeV-A3 infection. All children had low NATs at disease onset and high NATs after infection during infancy. At age 3 years, all 16 patients tested had high NATs (≥1:512) against PeV-A3 indicating that specific PeV-A3 NATs persist into childhood.

DOI： 10.1097/INF.0000000000002245

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Netherlands  

Japanese cedar (Cryptomeria japonica) pollinosis (JCP), affecting more than a quarter of the Japanese population, is a significant public health problem, due to its negative impact on daily activity. JCP patients have used the four-stage daily pollen deposition information based on the pollen monitoring over 20 years. However, the procedure for monitoring pollen was recently changed dramatically, to hourly average pollen concentration monitoring. In that type of monitoring, JCP patients cannot identify pollen exposure level because the relationship between hourly average pollen concentration and daily pollen deposition is unclear. Based on the parallel monitoring of concentration and deposition counts that we performed in Niigata prefecture, Eastern Japan, we found that the relationship between the daily pollen deposition (pollen cm−2 day−1) and the daily-average pollen concentration (pollen m−3) calculated from hourly average pollen concentration was not only statistically significant but also consistent with the aerodynamic properties of pollen. Using the relationship, we proposed new range criteria of hourly average pollen concentrations corresponding to the four stages of pollen deposition. Additionally, the conversion of pollen deposition to pollen concentration made the long-term trend analysis of the daily-average pollen concentration possible in this study area, and an increasing trend was identified at one site.

DOI： 10.1007/s10453-018-9511-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CAMBRIDGE UNIV PRESS  

Human parechoviruses (HPeVs) mainly infect young children, causing mild gastrointestinal and respiratory diseases; however, HPeV type 3 (HPeV3) causes severe systemic diseases in young infants. To clarify the characteristics of HPeV infections from the aspects of seropositivity and epidemiology, we measured neutralizing antibody titres against HPeVs in individuals of in different age groups and isolated HPeVs from various clinical specimens in Niigata, Japan. The seropositivity to HPeV1, 3, and 6 was higher in older age group. HPeV1 and HPeV6 seropositivities were maintained in adults, whereas HPeV3 seropositivity was significantly lower in subjects aged &gt;40 years (P &lt; 0.001, P = 0.003). This result suggests that adults have increased susceptibility to HPeV3 as they lack neutralizing antibodies against HPeV3. Of the HPeV isolates, HPeV1 and HPeV6 frequently caused gastrointestinal symptoms. Moreover, gastroenteritis patients with HPeV1 and HPeV6 were mainly aged 6 months-1 year and 52 years, respectively. In contrast, only HPeV3 was isolated from neonates and young infants with sepsis or sepsis-like syndrome, often with respiratory symptoms. These results suggest that clinical symptoms are clinically related to HPeV genotype and patients' age.

DOI： 10.1017/S0950268816001795

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO LTD  

During the 2014 human parechovirus type 3 (HPeV3) epidemic in Niigata, Japan, this prospective observational study identified HPeV3 from 43/85 (51%) febrile young infants &lt;4 months using PCR analysis of serum (n = 42) and/or cerebrospinal fluid (CSF) (n = 32) and genetic sequencing of the VP1 region of HPeV3. HPeV3-infected patients (median age, 32 days; range, 4-113 days) were diagnosed as having sepsis (79%), sepsis-like syndrome (19%), or encephalitis with septic shock (2%). Other than fever, mottled skin (67%) was significantly more frequent in HPeV3-infected patients than other virus-infected patients (P = 0.005). The rate of HPeV3 RNA detection in CSF without pleocytosis was high (88%; 28/32). Among the 32 patients whose serum and CSF samples were available, all patients were positive for serum PCR; however, 4 (12%) patients were negative for CSF PCR. Serum HPeV3 RNA level on admission was associated with younger age (P = 0.002), bad temper (P = 0.041), and grunting (P = 0.008). Among 6 patients with sequential data on serum HPeV3 RNA level, levels decreased rapidly without specific therapy. In conclusion, serum samples at disease onset are the most useful compared to CSF in detection of HPeV RNA and serum HPeV3 RNA level on admission was associated with important clinical manifestations in HPeV3-infected patients. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jinf.2015.10.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study
many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.

DOI： 10.1159/000443727

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CENTERS DISEASE CONTROL  

Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (&gt;= 1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p&lt;0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (&lt;= 1:16) at onset and persistently high NATs (&gt;= 1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients.

DOI： 10.3201/eid2111.150267

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Human parechovirus type 3 (HPeV3) epidemics occur worldwide and can lead to severe disease in neonates and young infants. Little is known about the source of HPeV3 infection.
Objectives: To investigate the source of HPeV3 infection and the role of asymptomatic children in the families of infected children.
Study design: During a 2014 HPeV3 epidemic in Niigata, Japan, we analyzed (1) clinical information on sick contacts for 43 neonates and young infants with HPeV3-related disease diagnosed by PCR analysis of serum and/or cerebrospinal fluid and (2) stool samples from symptomatic and asymptomatic siblings/cousins of index patients. To confirm transmission, the P1 (VP0, VP3, and VP1) and 3D(pol) regions of HPeVs were sequenced and analyzed.
Results: Sick contact with family members was confirmed for 51% (n = 22) of patients. Among the 30 symptomatic family members, 67% (n = 20) were siblings, 20% (n = 6) were mothers, and 13% (n = 4) were other relatives. Stool samples from symptomatic and asymptomatic siblings/cousins of 4 HPeV3-infected patients yielded positive results for HPeVs on PCR analysis. Furthermore, the P1 and 3Dpol nucleotide sequences of family members were 100% identical to those of the respective index cases.
Conclusions: Identification of genetically identical virus from HPeV3-infected patients and asymptomatic children in their families suggests that the latter are a source of infection in neonates and young infants with HPeV3-related diseases. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jcv.2015.07.300

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：新潟大学医学部保健学科  

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Other Link： http://hdl.handle.net/10191/38952

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL INST INFECTIOUS DISEASES  

DOI： 10.7883/yoken.65.268

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本臨床衛生検査技師会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL INST INFECTIOUS DISEASES  

DOI： 10.7883/yoken.65.270

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL INST INFECTIOUS DISEASES  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC TROP MED & HYGIENE  

A large-scale epidemic of chikungunya (CHIK) fever occurred in several Indian Ocean islands in 2004 and spread to India and Sri Lanka. In December 2006, a returnee to Japan from Sri Lanka developed an acute febrile illness. The patient was confirmed to have CHIK fever after reverse transcription-polymerase chain reaction, and specific IgM and IgG detection. CHIK virus was isolated from the serum specimen collected at the acute stage. The isolated virus developed two different sizes of plaques. Two sub-strains with different genetic and biological characteristics were obtained by plaque purification from one isolate. The entire genome was sequenced and phylogenetic analysis of the El genome showed that the sub-strains were of the Central/East African genotype, and were closely related to recent isolates in India. This is the first report of CHIK virus genome sequences isolated from a patient infected in Sri Lanka.

DOI： 10.4269/ajtmh.2009.09-0009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL INST INFECTIOUS DISEASES  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Reverse transcription-PCR targeting the VP0 gene of human parechoviruses (HPeVs) was used to identify two isolates from two Japanese children&apos;s stool specimens. Molecular analysis revealed that these isolates belonged to HPeV type 4, and their nucleotide identity in the P1 region was 85.0%.

DOI： 10.1128/JCM.00791-08

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CENTER DISEASE CONTROL  

Vero cells, we isolated a virus (NII561-2000) from a cerebrospinal fluid specimen of a 1-year-old girl with Reye syndrome. The determined amino acid sequence of the virus indicated that the isolate was a human parechovirus (HPeV), a member of Picornaviridae. Neutralization test showed that the NII561-2000 virus had distinct antigenicity to HPeV-1, HPeV-2, and HPeV-3, and that the sequence was distinct from these types as well as from HPeV-4 and HPeV-5. Thus, we propose the virus (NII561-2000) as the prototype of HPeV-6. We isolated 10 NII561-2000-related viruses, 14 HPeV-1, 16 HPeV-3, and 1 HPeV-4 of 41 HPeVs from various clinical samples collected in Niigata, Japan. Clinical symptoms of the persons infected with the NII5612000-related viruses were infectious gastroenteritis, rash, upper respiratory tract infection, and paralysis, in addition to Reye syndrome in the 1-year-old girl.

DOI： 10.3201/eid1306.060896

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL INST INFECTIOUS DISEASES  

Highly active antiretroviral therapy (HAART) can suppress human immunodeficiency virus type 1 (HIV-1) replication and plasma HIV-1 to below detectable levels. However, HAART becomes ineffective when drug-resistant viruses emerge during HAART. Monitoring drug-resistance mutations in viruses is necessary for selecting new drugs or therapies effective at inhibiting such HIV-1 variants. Most laboratories in Japan perform the tests using in-house protocols. However, the quality of these tests has never been assessed. Our study assessing the accuracy and reliability of HIV-1 genotypic drug-resistance testing in 15 laboratories in Japan revealed that the quality was very high (97.3% accurate). The errors, though rare, were caused by human errors, poor electropherograms, and the use of inadequate primers. Here, we propose troubleshooting procedures to improve testing accuracy and reliability in Japan.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：National Institute of Infectious Diseases  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：National Institute of Infectious Diseases  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (other)   Publisher：医薬の門社  

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