Proposal for the Recognition of a New Disease Concept from Japan: Parechovirus A3-Associated Myalgia.

Parechovirus A3 (PeVA3) was first reported in 2004 and has been recognized as a causative agent of mild and severe infectious diseases in children. We first reported an outbreak of PeVA3-associated myalgia (PeVA3-M) in Yamagata, Japan, in 2008. We have repeatedly observed PeVA3-M cases in 2011, 2014, and 2016, and identified the first child case in 2014.

Seroprevalence of parechovirus A1, A3 and A4 antibodies in Yamagata, Japan, between 1976 and 2017.

Although new parechovirus A (PeVA) types, including parechovirus A3 (PeVA3) and PeVA4, have been reported in this century, there have not yet been any seroepidemiological studies on PeVA over a period of several decades. The authors hypothesize that PeVA3 and PeVA4 emerged recently. The aim was to clarify changes in the seroprevalence of PeVA1, PeVA3 and PeVA4.

Detection of Tick-Borne Pathogens in Ticks from Dogs and Cats in the Yamagata Prefecture of Japan in 2018.

Companion animals can become infected with tick-borne diseases (TBDs) becoming a reservoir for human transfer, thereby damaging human health. To evaluate whether companion animals are infested with ticks harboring human TBD pathogens, we detected TBD pathogens in ticks collected from dogs and cats brought to animal hospitals in the Yamagata prefecture of Japan. An investigation of 164 adult ticks collected from 88 dogs and 41 cats between March and July 2018 revealed that this region was dominated by three tick species, Ixodes ovatus (n = 95, 57.

Longitudinal epidemiology of human coronavirus OC43 in Yamagata, Japan, 2010-2017: Two groups based on spike gene appear one after another.

Human coronavirus OC43 (HCoV-OC43) is divided into genotypes A to H based on genetic recombination including the spike (S) gene. To investigate the longitudinal transition of the phylogenetic feature of the HCoV-OC43 S gene in a community, phylogenetic analysis of the S1 region of the S gene was conducted using 208 strains detected in Yamagata during 2010 to 2017 with reference strains of the genotype. The S1 sequences were divisible into four groups: A to D.

Influenza A(H1N1)pdm09 virus exhibiting reduced susceptibility to baloxavir due to a PA E23K substitution detected from a child without baloxavir treatment.

Human-to-human transmission of PA I38 mutant influenza A(H3N2) viruses with reduced baloxavir susceptibility has been reported in Japan. In December 2019, we detected a PA E23K mutant A(H1N1)pdm09 virus from a child without baloxavir treatment. The PA E23K mutant virus exhibited reduced baloxavir susceptibility but remained susceptible to neuraminidase inhibitors.

Heparan sulfate attachment receptor is a major selection factor for attenuated enterovirus 71 mutants during cell culture adaptation.

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). However, this infection is sometimes associated with severe neurological complications. Identification of neurovirulence determinants is important to understand the pathogenesis of EV71.

Antigenic changes among the predominantly circulating C/Sao Paulo lineage strains of influenza C virus in Yamagata, Japan, between 2015 and 2018.

Influenza C virus is a pathogen that causes acute respiratory illness in children and results in the hospitalization of infants. The antigenicity of the hemagglutinin esterase (HE) glycoprotein is highly stable, and it is not yet known whether antigenic changes contribute to the worldwide transmission and the occurrence of outbreaks of influenza C virus. Here, we performed antigenic analysis of 84 influenza C viruses isolated in Yamagata, Japan, during a 4-year period from 2015 to 2018 and analyzed sequence data for strains of the virus from Japan and many other parts of the world.

Development of an Enterovirus 71 Vaccine Efficacy Test Using Human Scavenger Receptor B2 Transgenic Mice.

Enterovirus 71 (EV71) is a causative agent of hand-foot-mouth disease, and it sometimes causes severe neurological disease. Development of effective vaccines and animal models to evaluate vaccine candidates are needed. However, the animal models currently used for vaccine efficacy testing, monkeys and neonatal mice, have economic, ethical, and practical drawbacks.

T serotyping of group a streptococcus isolated from patients with pharyngitis or streptococcal toxic shock syndrome in Japan between 2005 and 2017.

Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017.

Systematic evaluation of suspension MDCK cells, adherent MDCK cells, and LLC-MK2 cells for preparing influenza vaccine seed virus.

Suspension Madin-Darby canine kidney (MDCK) cells (MDCK-N), adherent MDCK cells (MDCK-C), and adherent rhesus monkey kidney LLC-MK2 cells (LLC-MK2D) were systematically evaluated for the preparation of influenza vaccine seed viruses for humans on the basis of primary virus isolation efficiency, growth ability, genetic stability of the hemagglutinin (HA) and neuraminidase (NA) genes, and antigenic properties in hemagglutination inhibition (HI) test of each virus isolate upon further passages. All the subtypes/lineages of influenza viruses (A(H1N1), A(H1N1)pdm09, A(H3N2), B-Victoria, and B-Yamagata) were successfully isolated from clinical specimens by using MDCK-N and MDCK-C, whereas LLC-MK2D did not support virus replication well. Serial passages of A(H1N1) viruses in MDCK-N and MDCK-C induced genetic mutations of HA that resulted in moderate antigenic changes in the HI test.

Nationwide Molecular Epidemiology of Measles Virus in Japan Between 2008 and 2017.

Genotyping evidence that supports the interruption of endemic measles virus (MV) transmission is one of the essential criteria to be verified in achieving measles elimination. In Japan since 2014, MV genotype analyses have been performed for most of the measles cases in prefectural public health institutes nationwide. With this strong molecular epidemiological data, Japan was verified to have eliminated measles in March, 2015.

Scrub typhus caused by Shimokoshi type Orientia tsutsugamushi showing variant 56-kDa type-specific antigen gene sequence in Tohoku region, Japan.

In 2018, a patient was diagnosed with Shimokoshi type scrub typhus in Yamagata Prefecture, Japan. The causative pathogen was likely a variant type because 43 (8.3%) of 521 deduced amino acid sequences of the 56-kDa type-specific antigen (TSA) were different from those of the Shimokoshi prototype strain.

Polyclonal spread of multiple genotypes of Mycoplasma pneumoniae in semi-closed settings in Yamagata, Japan.

Purpose: To clarify the spread of Mycoplasma pneumoniae infections in semi-closed settings such as schools and family homes using molecular typing methods.

Methodology: We retrospectively searched for school- and family-based clusters of M. pneumoniae infections based on information regarding patients from whom M.

Asymmetric N-H Insertion Reaction with Chiral Aminoalcohol as Catalytic Core of Cinchona Alkaloids.

In order to develop an efficient organocatalyst for the enantioselective N-H insertion reaction via carbene/carbenoid, the catalytic core of the cinchona alkaloids was investigated. According to our working hypothesis of an eight-membered ring transition state in the N-H insertion reaction, two pairs of enantiomers related to 2-amino-1-phenylethanol were investigated for their chiral inducing potential. Since both (1R,2S)-isomers gave the N-phenyl-1-phenylglycine derivative enriched in the R-form, while their enantiomers gave the S-form, the 2-amino-1-phenylethanol structure is concluded to be the catalytic core of the cinchona alkaloid in the enantioselective N-H insertion reaction via rhodium(II) carbenoid.

Longitudinal Epidemiology of Viral Infectious Diseases Combining Virus Isolation, Antigenic Analysis, and Phylogenetic Analysis as Well as Seroepidemiology in Yamagata, Japan, between 1999 and 2018.

We introduced a microplate method for virus isolation in the Department of Microbiology, Yamagata Prefectural Institute of Public Health (YPIPH) in 1999 in Yamagata, Japan. We have since carried out longitudinal epidemiological studies on viral infectious diseases, particularly respiratory viruses, combining traditional technologies such as virus isolation and serological techniques and newly developed molecular methods. Here, we provide an overview of our activities at YPIPH between 1999 and 2018.

Diversity of spotted fever group rickettsiae and their association with host ticks in Japan.

Spotted fever group (SFG) rickettsiae are obligate intracellular Gram-negative bacteria mainly associated with ticks. In Japan, several hundred cases of Japanese spotted fever, caused by Rickettsia japonica, are reported annually. Other Rickettsia species are also known to exist in ixodid ticks; however, their phylogenetic position and pathogenic potential are poorly understood.

Phylogenetic and antigenic analyses of coxsackievirus A6 isolates in Yamagata, Japan between 2001 and 2017.

Although coxsackievirus A6 (CV-A6) is generally recognized as a causative agent of herpangina in children, CV-A6 infections globally emerged as a new and major cause of epidemic hand-foot-and-mouth-diseases (HFMDs) around 2008. To clarify the longitudinal epidemiology of CV-A6, we carried out sequence and phylogenetic analyses for the VP1 and partially for the VP4-3D regions as well as antigenic analysis using 115 CV-A6 isolates and 105 human sera in Yamagata, Japan between 2001 and 2017. Phylogenetic analysis revealed that CV-A6 isolates were clearly divided into two clusters; strains in circulation between 2001 and 2008 and those between 2010 and 2017.

Nosocomial Mycobacterium tuberculosis transmission by brief casual contact identified using comparative genomics.

This paper reports a case of nosocomial transmission of Mycobacterium tuberculosis by brief casual contact. Routine variable number tandem repeat typing in Yamagata Prefecture, Japan found that M. tuberculosis clinical isolates from two patients showed indistinguishable genotypes.