{"created":"2021-03-01T06:18:55.553207+00:00","id":2319,"links":{},"metadata":{"_buckets":{"deposit":"77fb97c8-6c00-431c-b100-0f85da9d1052"},"_deposit":{"id":"2319","owners":[],"pid":{"revision_id":0,"type":"depid","value":"2319"},"status":"published"},"_oai":{"id":"oai:repository.dl.itc.u-tokyo.ac.jp:00002319","sets":["125:353:354","9:233:280"]},"item_7_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"小児におけるノロウィルス感染症 : 迅速診断法の開発と分子疫学的特徴に関する研究"}]},"item_7_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-03-23","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{}]}]},"item_7_date_granted_25":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2009-03-23"}]},"item_7_degree_grantor_23":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"University of Tokyo (東京大学)"}]}]},"item_7_degree_name_20":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_7_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Norovirus (NoV) is a major cause of non-bacterial acute gastroenteritis in infants and young children all over the world. It is reported that NoV causes up to 200,000 deaths of children in developing countries, and 64,000 episodes of diarrhea requiring hospitalization among children in industrialized countries. Although NoV is such a common infectious disease and more than 30 years have passed since its discovery, the diagnosis of this viral infection has remained difficult in the clinical setting. This is mainly due to the unavailability of a cell culture system to cultivate this virus, which has hampered the development of immunological assays. In consequence, the natural course and pathogenesis of NoV infection have not been fully understood to date.//This research is divided into four chapters. In the first chapter, I describe the development of immunochromatography (IC) for NoV as an alternative rapid detection method. Polyclonal antibodies were raised in rabbits against recombinant virus-like particles (rVLPs) of the prevalent NoV genotypes, namely GII/3 and GII/4, and were applied on to the IC kit as the capture and detection antibodies. This kit was evaluated for its reactivity to rVLPs and for the detection of natural viruses in stool samples collected from diarrheal children compared to the results by RT-PCR. In the prospective assessment, the kit showed agreement rate of 84.1%, sensitivity of 69.8% and specificity of 93.7%. Genotyping of the RT-PCR positive samples by sequence analysis revealed that some heterogeneous genotypes were also detected, while some in homogenous genotypes occasionally showed false negative records resulting in lower sensitivity. No cross reactivity with other common viral pathogens was observed. Inaddition, the detection limit of viral load was as small as approximately 106-7 copies/g of stool. Taken together, using the current IC in the screening process for NoV with simple laboratory support is justified .//In the second chapter, I describe detection of NoV RNA in samples other than stool from children with acute gastroenteritis to elucidate potential extraintestinal involvement of NoV gastroenteritis as an unseen feature of its pathogenesis. NoV RNA was detected by seminested RT-PCR in serum samples from 6 out of 39 (15.4%) of the NoV gastroenteritis patients. Neither of the two cerebral spinal fluid samples was positive for NoV RNA. The serum-positive patients showed neurological complications more frequently than the serum-negative patients (p=0.028). The viral load in the stools of the serum-positive patients was not significantly greater than that of the serum-negative patients (median: 9.8×109 copies/g versus 1.1×109 copies/g (p=0.117)), and the viral load in the serum and stools of the serum-positive patients did not correlate.//However, genotypes of the NoV in stools and serum from the same patient matched completely (GII/3:1, GII/4: 5) with high homology ranging from 99.2% to 100% between the paired samples, demonstrating that RNA in sera originated from the intestines.//In the third chapter, I describe the prevalence and changing distribution ofdiarrheal viruses in children attending a day care center (DCC) in Tokyo, Japan. No Vemerged as the most predominant diarrheal virus in children attending a DCC (p<0.01), while the overall detection rate of viruses decreased (p<0.001) in the 6 years since the first study was conducted in the same DCC using the same detection method. Eighteen out of 20 children experienced No V GII infection during one year, including multiple genotypes infection and re-infection of the same genotype. There was no significantdifference in norovirus load between symptomatic and asymptomatic children (median : 1.5×106 copies/g versus 2.6×104 copies/g (p=0.6)). Sequencing and quantitative analysis revealed that an asymptomatic child excreting an insignificant amount of virus (4.7×104 copies per gram of stool) may cause a major outbreak of NoV in a semiclosed setting such as a DCC. In the final chapter, I describe the prevalence and molecular epidemiological characters of NoV in children hospitalized with acute gastroenteritis in Kandy, Sri Lanka. NoVs were first detected in samples from Sri Lankan children, and their nucleotide data were deposited in the GenBank. NoV was ranked as the second most common causative virus accounting for 10.5% of the cases after group A rotavirus. Among 33 patients showing monoinfection with NoV, the main clinical manifestations observed were diarrhea (100%), vomiting (72.7%), and body temperature ≥ 37.5℃ (51.5%). Regarding the severity of infected patients, NoV showed a high severity score comparable to group A rotavirus and mixed infection group. Each clinical symptom showed no statistically significant difference between NoV infection and other diarrheal viruses. A distinct peak of NoV was observed in the dry and cool season of the year. Great genetic diversity of NoV was recognized, encompassing five genotypes including rare GII/9 and GII/16. GII/3 was the most predominant genotype (22 of 38, 57.9%), showing high homology with globally distributed strains. In conclusion, a simple and easily performable detection kit with an immunochromatographic system was successfully developed to improve notification of NoV infection in clinical practice. It was suggested that NoV spreads from the intestines to the blood stream, possibly accounting for extraintestinal complications of NoV gastroenteritis. Asymptomatic children were suspected to be an important source ofNoV outbreak, emphasizing the importance of standard precautions. A significant disease burden of NoV infection was recognized in Sri Lanka, where no report of NoV had been made before this study. Although the numbers of molecular epidemiological studies have been increased dramatically over the years, continuous monitoring and detailed genetic analysis are necessary to assess the full implication of the global evolution of this virus.","subitem_description_type":"Abstract"}]},"item_7_dissertation_number_26":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第24872号"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"6520","nameIdentifierScheme":"WEKO"}],"names":[{"name":"高梨, さやか"}]}]},"item_7_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15083/00002313","subitem_identifier_reg_type":"JaLC"}]},"item_7_select_21":{"attribute_name":"学位","attribute_value_mlt":[{"subitem_select_item":"doctoral"}]},"item_7_text_22":{"attribute_name":"学位分野","attribute_value_mlt":[{"subitem_text_value":"Medical Science (医学)"}]},"item_7_text_24":{"attribute_name":"研究科・専攻","attribute_value_mlt":[{"subitem_text_value":"Department of Reproductive, Developmental and Aging Sciences, Graduate School of Medicine (医学系研究科生殖・発達・加齢医学専攻)"}]},"item_7_text_27":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_value":"博医第3292号"}]},"item_7_text_4":{"attribute_name":"著者所属","attribute_value_mlt":[{"subitem_text_value":"東京大学大学院医学系研究科生殖・発達・加齢医学専攻小児科学"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Takanashi, Sayaka"}],"nameIdentifiers":[{"nameIdentifier":"6519","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-05-31"}],"displaytype":"detail","filename":"41_takanashi.pdf","filesize":[{"value":"929.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"41_takanashi.pdf","url":"https://repository.dl.itc.u-tokyo.ac.jp/record/2319/files/41_takanashi.pdf"},"version_id":"c80f4e2e-faee-4dd1-a3fa-f9510a2e6b7b"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Norovirus Infection in Children : Studies on Rapid Detection Method and Molecular Epidemiological Characters","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Norovirus Infection in Children : Studies on Rapid Detection Method and Molecular Epidemiological Characters"}]},"item_type_id":"7","owner":"1","path":["280","354"],"pubdate":{"attribute_name":"公開日","attribute_value":"2012-03-01"},"publish_date":"2012-03-01","publish_status":"0","recid":"2319","relation_version_is_last":true,"title":["Norovirus Infection in Children : Studies on Rapid Detection Method and Molecular Epidemiological Characters"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2022-12-19T03:43:57.943033+00:00"}