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Sakata M.,Kitasato Institute Research Center for Biologicals | Sakata M.,Japan National Institute of Infectious Diseases | Nakayama T.,Kitasato Institute for Life science
Vaccine | Year: 2011

Wild-type rubella viruses grow well at 39 °C (non-temperature sensitivity: non- ts), while vaccine strains do not (temperature sensitivity: ts). Histidine at position 1042 of the p150 region of the KRT vaccine strain was found to be responsible for ts, while wild-type viruses had tyrosine at position 1042 (Vaccine 27; 234-42, 2009). The point-mutated virus (Y1042H) based on the wild-type unexpectedly showed little reduction in growth at 39 °C. In this report, several recombinant viruses were characterized, and point-mutated Y1042H together with the p90 region of KRT significantly reduced virus growth, compared to the parental wild-type virus. There was one amino acid difference at position 1497 of the helicase domain in the p90 region. Double mutation involving both positions 1042 and 1497 markedly reduced virus growth at 39 °C, but single substitution at 1497 did not. The other vaccine strain (TO-336vac) was investigated, and serine at position 1159 of the protease domain in p150 was a crucial amino acid for ts and non- ts characteristics among four amino acid substitutions between TO-336vac and the wild-type. Our results suggest that protease and helicase domains in non-structural protein were consistent with ts phenotype, possibly related to the attenuation process of wild-type viruses. © 2010 Elsevier Ltd.

Takayama Y.,Kitasato University | Okamoto R.,Kitasato University | Sunakawa K.,Kitasato Institute for Life science
Journal of the Formosan Medical Association | Year: 2010

Background/Purpose: To evaluate the epidemiology, clinical features, and microbiological features (including antibiotic susceptibility) of infective endocarditis (IE) at Kitasato University Hospital, Japan. Methods: We retrospectively analyzed 153 patients (155 episodes) with definite IE according to the Duke criteria, who presented over a 17-year period. The minimum inhibitory concentrations of antibiotics for cultured causative microorganisms were also examined. Results: Viridans group streptococci were the most common pathogens (36.8%, 57 episodes), followed by Staphylococcus aureus [21.3%, 33 episodes, including 10 episodes due to methicillin-resistant S. aureus (MRSA)]. Thirty-nine of the 40 strains of viridans streptococci were fully susceptible to penicillin. Comparison of IE due to methicillin-sensitive S. aureus (MSSA) and MRSA showed that the latter had a higher mortality rate (34.8%, 8/23 vs. 70.0%, 7/10). Compared with MSSA, IE caused by MRSA was significantly more likely to be related to nosocomial infection (10/10, p < 0.001), hemodialysis (4/10, 40.0%, p = 0.005), and surgery or intravascular catheter insertion (8/10, 80.0%, p = 0.007). There was a significantly higher mortality rate in non-operated (15/43, 34.9%) than in operated (2/21, 9.5%) (p < 0.001) elderly patients. In 92/155 episodes (59.4%), antibiotics were given before blood cultures were obtained. Culture-negative IE occurred in 20.7% (19/92) of patients on antibiotics versus 6.3% (4/63) of those not on antibiotics (p = 0.02). Of 155 episodes of IE, 34 (21.9%) were fatal and staphylococcal had significantly higher mortality than streptococcal IE [(19/40, 47.5%) vs. (7/72, 9.7%); p < 0.001]. Conclusion: The most frequently isolated pathogens were viridans group streptococci, which differed from other recent studies. In the present study, no penicillin-resistant strains were detected and there was a higher mortality rate for IE caused by MRSA than MSSA. IE should be considered in MRSA patients with the following risk factors: nosocomial infection, hemodialysis, and surgery or intravascular catheter insertion. © 2010 Elsevier & Formosan Medical Association.

Jin L.,Public Health England | Orvell C.,University of Stockholm | Myers R.,Public Health England | Rota P.A.,Centers for Disease Control and Prevention | And 4 more authors.
Reviews in Medical Virology | Year: 2015

The WHO recently proposed an updated nomenclature for mumps virus (MuV). WHO currently recognizes 12 genotypes of MuV, assigned letters from A to N (excluding E and M), which are based on the nucleotide sequences of small hydrophobic (SH) and haemagglutinin-neuraminidase (HN) genes. A total of 66 MuV genomes are available in GenBank, representing eight of the 12 genotypes. To complete this dataset, whole genomes of seven isolates representing six genotypes (D, H, I, J, K and L) and one unclassified strain were sequenced. SH and HN genes of other representative strains were also sequenced. The degree of genetic divergence, predicted amino acid substitutions in the HN and fusion (F) proteins and geographic distributions of MuV strains were analysed based on the updated dataset. Nucleotide heterogeneity between genotypes reached 20% within the SH gene, with a maximum of 9% within the HN gene. The geographic and chronologic distributions of the 12 genotypes were summarised. This review contributes to our understanding of strain diversity for wild type MuV, and the results support the current WHO nomenclature. © 2014 John Wiley & Sons, Ltd.

Nakayama T.,Kitasato Institute for Life science | Ishii K.J.,Japan National Institute of Biomedical Innovation | Ishii K.J.,Osaka University | Ihara T.,National Mie Hospital
Vaccine | Year: 2012

IgG subclass antibody responses are not fully understood. Alum-adjuvanted H5N1whole virion inactivated vaccine (WIV), a genetically reassortant vaccine seed strain originating from H5N1/A/Vietnam/1194/2004 and PR-8, induced significantly stronger antibody responses in neutralizing antibodies in children. In this report, IgG subclass antibody responses were investigated, and most serum samples were positive for IgG1 antibody before immunization. A significant response (more than 4-fold increase) of IgG1 antibody was observed in 67/193 (34.7%) and that of gG4 antibodies in 42/193(21.8%). Children <4 years of age showed a significant increase in IgG subclass antibodies but those ≥4 years showed lower responses. Alum- adjuvanted H5N1WIV induced an efficient immune response in young children especially <4 years. © 2012 Elsevier Ltd.

Muta H.,Iizuka City Hospital | Ihara T.,National Hospital Organization | Nakayama T.,Kitasato Institute for Life science
Vaccine | Year: 2015

Objective: The purpose of this study was to determine the risk of aseptic meningitis after mumps vaccination in younger children compared with older children. Methods: This prospective cohort study included a total of 21,465 children under 18 years of age who had received the first dose of three of the Japanese mumps monovalent vaccine. We compared the cumulative incidence of aseptic meningitis for 30 days after vaccination among the following age groups: ≤1, 2, 3-4, and ≥5 years old. We also investigated the cumulative incidence of salivary gland swelling, a fever (≥38. °C) lasting at least 3 days during the 10 to 25 days following immunization, vomiting of 3 times or more, headache, and seizure. Results: A total of 10 aseptic meningitis, 551 salivary gland swelling, 844 fevers, 669 vomiting, 757 headaches, and 29 seizure cases were identified. The cumulative incidence of aseptic meningitis increased with age (0.016%, 0.021%, 0.066%, and 0.096%, respectively). Statistical significance was observed between children ≥3 years old and those <3 years of age [0.078% vs. 0.018%, RR 4.35 (95% CI 1.05-18.2), p= 0.04]. The cumulative incidence of salivary gland swelling also increased with age (1.8%, 3.0%, 3.5%, and 4.5%, respectively). For non-specific adverse events, the cumulative incidence of fever or seizure decreased with age. In contrast, the cumulative incidence of headache increased with age. The cumulative incidence of vomiting was similar among children ≤4 years of age; however, that in those children ≥5 years old was significantly lower. Conclusions: The first dose of mumps vaccine that is currently available for use in Japan may be administered in children less than 3 years of age in order to complicate a less aseptic meningitis after immunization. © 2015 Elsevier Ltd.

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