著者

Noriko Nakajima Satoru Hata Yuko Sato Minoru Tobiume Harutaka Katano Keiko Kaneko Noriyo Nagata Michiyo Kataoka Akira Ainai Hideki Hasegawa Masato Tashiro Makoto Kuroda Tamami Odai Nobuyuki Urasawa Tomoyoshi Ogino Hiroaki Hanaoka Masahide Watanabe Tetsutaro Sata

出版者

National Institute of Infectious Diseases

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

vol.63, no.1, pp.67-71, 2010-01-29 (Released:2022-03-31)

参考文献数

1

被引用文献数

2 57

---

We report the pathological and virological findings of the first autopsy case of the 2009 pandemic influenza (A/H1N1pdm) virus infection in Japan. A man aged 33 years with chronic heart failure due to dilated cardiomyopathy, mild diabetes mellitus, atopic dermatitis, bronchial asthma, and obesity died of respiratory failure and multiple organ dysfunction syndrome. Macroscopic examination showed severe plumonary edema and microscopically the lung sections showed very early exudative-stage diffuse alveolar damage (DAD). Immunohistochemistry revealed proliferation of the influenza (A/H1N1pdm) virus in alveolar epithelial cells, some of which expressed SAα2-3Gal on the cell surface. Influenza (A/H1N1pdm) virus genomic RNA and mRNA were also detected in alveolar epithelial cells. Real-time PCR revealed 723 copies/cell in the left lower lung section from which the influenza (A/H1N1pdm) virus was isolated. Electron microscopic analysis revealed filamentous viral particles in the lung tissue. The concentrations of various cytokines/chemokines in the serum and the autopsied lung tissue were measured. IL-2R, IL-6, IL-8, IL-10, IFN-α, MCP-1, and MIG levels were elevated in both. These findings indicated a case of viral pneumonia caused by influenza (A/H1N1pdm) virus infection, showing characteristic pathological findings of the early stage of DAD.

著者

Keisuke Nonaka Yoko Matsuda Mototsune Kakizaki Shoichiro Takakuma Akihiko Hamamatsu Yasuhiro Sakashita Tomoyasu Matsubara Shigeo Murayama Toshiyuki Ishiwata Noriko Yamanaka Mitsuyo Itabashi Takashi Takei Noriko Nakajima Hideki Hasegawa Tomio Arai

出版者

National Institute of Infectious Diseases

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

vol.72, no.5, pp.347-349, 2019 (Released:2019-09-19)

参考文献数

10

被引用文献数

7 8

---

An 84-year-old man with chronic renal failure, anemia, and diabetes was admitted for hemodialysis initiation. His vital signs were stable until the eighteenth hospital day, before acquiring an influenza A virus infection. Three days later, he died of septic shock with severe liver impairment. His leukocyte count, prothrombin time (PT-INR), and liver enzyme levels such as aspartate transaminase and alanine aminotransferase, were significantly increased. Hypercytokinemia was also observed. Autopsy revealed bilateral diffuse pneumonia with neutrophil infiltration. The liver showed extensive centrilobular hepatocyte necrosis. Immunohistochemistry for influenza A nucleoprotein revealed positivity in the ciliated columnar epithelium of the bronchi and negativity in the trachea, lungs, and liver. Hypoxic hepatitis is characterized by an abrupt and massive increase in aminotransferase levels (> 20 times upper normal limit) due to anoxic centrilobular hepatocyte necrosis. The occurrence of hypoxic hepatitis requires a pre-existing, chronic condition, such as anemia, causing reduced oxygen supply to the liver, followed by an acute decrease in hepatic oxygen supply, such as septic shock. Therefore, this report suggests that hypoxic hepatitis can be an important causative factor for acute liver failure associated with influenza virus infection.

著者

Itoe Iizuka Yasushi Ami Yuriko Suzaki Noriyo Nagata Shuetsu Fukushi Momoko Ogata Shigeru Morikawa Hideki Hasegawa Masashi Mizuguchi Ichiro Kurane Masayuki Saijo

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

vol.70, no.4, pp.408-415, 2017 (Released:2017-07-24)

参考文献数

20

被引用文献数

3 27

---

Monkeypox virus (MPXV) causes human monkeypox (human MPX), which is a similar disease to smallpox in humans. A previous study showed that a single vaccination of monkeys with LC16m8, a highly attenuated smallpox vaccine, protected them from MPX from 4-5 weeks post-vaccination. In this study, we evaluated the long-term efficacy of a single vaccination with LC16m8 in a nonhuman primate model of MPXV infection. The monkeys were inoculated with either LC16m8, Lister (parental strain of LC16m8), or a mock-up vaccine, and then challenged with MPXV via a subcutaneous route, at 6 and 12 months after vaccination, which we compared with either Lister or the mock-up vaccination. The LC16m8 monkeys exhibited almost no MPX-associated symptoms, whereas most of the naïve monkeys died. LC16m8 generated the protective memory immune response against MPXV, as suggested by the immediate viremia reduction and the response of the IgG antibody. The results demonstrated that the vaccination of monkeys with a single dose of LC16m8 provided durable protection against MPXV for longer than one year after immunization. The results suggest that the vaccination of humans with LC16m8 could induce long-term protection against MPXV infection.

著者

Yuki Higashimoto Masaru Ihira Yoshiki Kawamura Masato Inaba Kazuya Shirato Tadaki Suzuki Hideki Hasegawa Tsutomu Kageyama Yohei Doi Tadayoshi Hata Tetsushi Yoshikawa

出版者

Fujita Medical Society

雑誌

Fujita Medical Journal (ISSN:21897247)

巻号頁・発行日

pp.2022-003, (Released:2022-07-22)

参考文献数

38

---

Objectives: To establish a point-of-care test for coronavirus disease 2019 (COVID-19), we developed a dry loop-mediated isothermal amplification (LAMP) method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.Methods: We carried out reverse transcription (RT)-LAMP using the Loopamp SARS-CoV-2 Detection kit (Eiken Chemical, Tokyo, Japan). The entire mixture, except for the primers, is dried and immobilized inside the tube lid.Results: To determine the specificity of the kit, 22 viruses associated with respiratory infections, including SARS-CoV-2, were tested. The sensitivity of this assay, determined by either a real-time turbidity assay or colorimetric change of the reaction mixture, as evaluated by the naked eye or under illumination with ultraviolet light, was 10 copies/reaction. No LAMP product was detected in reactions performed with RNA from any pathogens other than SARS-CoV-2. After completing an initial validation analysis, we analyzed 24 nasopharyngeal swab specimens collected from patients suspected to have COVID-19. Of the 24 samples, 19 (79.2%) were determined by real-time RT-PCR analysis as being positive for SARS-CoV-2 RNA. Using the Loopamp SARS-CoV-2 Detection kit, we detected SARS-CoV-2 RNA in 15 (62.5%) of the 24 samples. Thus, the sensitivity, specificity, positive predictive value, and negative predictive values of the Loopamp 2019-CoV-2 detection reagent kit were 78.9%, 100%, 100%, and 55.6%, respectively.Conclusions: The dry LAMP method for detecting SARS-CoV-2 RNA is fast and easy to use, and its reagents can be stored at 4°C, solving the cold chain problem; thus, it represents a promising tool for COVID-19 diagnosis in developing countries.

著者

Tsuyoshi Sekizuka Kentaro Itokawa Masumichi Saito Michitsugu Shimatani Shutoku Matsuyama Hideki Hasegawa Tomoya Saito Makoto Kuroda

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

pp.JJID.2021.844, (Released:2022-02-28)

参考文献数

12

被引用文献数

22

---

Prominent genomic recombination has been observed between the Delta and Alpha variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from clinical specimens in Japan. Interestingly, the recombination variant detected in this study carries a spike protein identical to the one in the domestic Delta variant, thereby suggesting that further risks would not be concerned with infectivity and immune escape. The recombinant has been classified as XC lineage in the PANGOLIN database. It is necessary to intensively study such marked genetic variations and characterize the emerging variants after careful verification of their lineage and clade assignment.

著者

Emi Takashita Hiroko Morita Shiho Nagata Masayuki Shirakura Seiichiro Fujisaki Hideka Miura Ikuyo Takayama Tomoko Arita Yasushi Suzuki Masaoki Yamaoka Taichiro Tanikawa Ryota Tsunekuni Junki Mine Saki Sakuma Yuko Uchida Akihiro Shibata Mari Iwanaka Noriko Kishida Kazuya Nakamura Tsutomu Kageyama Shinji Watanabe Hideki Hasegawa The Influenza Virus Surveillance Group of Japan

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

pp.JJID.2021.751, (Released:2021-12-28)

参考文献数

15

被引用文献数

1

---

Circulation of avian influenza A viruses in poultry is a public health concern because these viruses may cause severe disease in humans and have the potential to become more transmissible among humans. Monitoring the susceptibility of these viruses to antivirals is important for influenza pandemic preparedness. However, information about their antiviral susceptibility is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: the M2 inhibitor amantadine; the neuraminidase inhibitors oseltamivir, peramivir, zanamivir, and laninamivir; and the RNA polymerase inhibitors baloxavir and favipiravir. Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess viral susceptibility to drugs revealed that these avian influenza A viruses are susceptible to neuraminidase inhibitors and RNA polymerase inhibitors. These results suggest that the neuraminidase inhibitors and the RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.

著者

Shin-ichi Tamura Akira Ainai Tadaki Suzuki Takeshi Kurata Hideki Hasegawa

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

vol.69, no.3, pp.165-179, 2016 (Released:2016-05-20)

参考文献数

98

被引用文献数

23 33

---

Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based on this parameter. Data suggest that adjuvant-combined nasal-inactivated vaccines have advantages over the current injectable vaccine because the former induce both S-IgA and serum IgG Abs. In addition, nasal-inactivated vaccines seem to be superior to the LAIV vaccines, because non-infectious preparations could be used in high-risk groups. Thus, the development of intranasal inactivated vaccines is recommended, because such vaccines are expected to improve the efficacy of influenza vaccines.

著者

Hanako Sekimukai Naoko Iwata-Yoshikawa Aiko Fukuma Syuetsu Fukushi Hideki Tani Kenichi Niikura Hideki Hasegawa Michiyo Kataoka Katsuhiko Arai Noriyo Nagata

雑誌

ConBio2017

巻号頁・発行日

2017-10-31

著者

Kiyoko Okamaoto Kazuya Shirato NagaNaganori Nao Shinji Saito Tsutomu Kageyama Hideki Hasegawa Tadaki Suzuki Shutoku Matsuyama Makoto Takeda

出版者

National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

雑誌

Japanese Journal of Infectious Diseases (ISSN:13446304)

巻号頁・発行日

pp.JJID.2020.108, (Released:2020-04-30)

参考文献数

11

被引用文献数

13 33

---

The COVID-19 outbreak caused by SARS-CoV-2 in Wuhan (China) in December 2019 is currently spreading rapidly and globally. We recently reported a laboratory diagnostic protocol for SARS-CoV-2 based on real-time RT-PCR assays using two primer sets, N and N2. On 30–31 January 2020, the protocol and reagents for these assays were distributed to local public health institutes and quarantine depots in Japan, and nationwide, SARS-CoV-2 diagnostic testing was started. For further validation, the assays were compared with the commercially available kits using SARS CoV-2 viral RNA and the clinical specimens obtained from COVID19-suspected individuals. The LightMix Modular SARS and Wuhan CoV E-gene (LN S&W-E) assay was highly sensitive for SARS-CoV-2, as was the N2 set, and both assays had perfectly consistent results with the clinical specimens. While the LM S&W-E set targets the highly conserved region of the E gene in SARS-CoV and SARS-CoV-2, the N2 set was designed to target the unique region in the SARS-CoV-2 N gene. Thus, the N2 set has high specificity and sensitivity for SARS-CoV-2 detection. These indicate that the protocol using the N and N2 sets is comparable to commercially available kits and is reliable for the laboratory diagnosis of COVID-19.