NATIONAL INSTITUTE OF INFECTIOUS DISEASE（PDF）

History

Immediately after World War II, Japan suffered from various infectious diseases caused by poor sanitation; infectious diseases such as tuberculosis, typhoid fever, dysentery, diphtheria, Japanese encephalitis, and parasitic infections were rampant, while many other infectious diseases were newly introduced from foreign countries. Under such circumstances, infectious disease control became a high-priority issue for establishing a safe and secure society in the developing nation. In 1947, the National Institute of Health (NIH), which was later renamed as the National Institute of Infectious Diseases, was established as a research institute attached to the Ministry of Health and Welfare for conducting (i) fundamental and applied research on infectious diseases and (ii) national test for lot release and development of antibiotics and vaccines.

In 1892, the Institute for Infectious Disease was founded as a private institute in attached to the Hygiene Society of Japan (Dr. Shibasaburo Kitasato was the founding dean). The institute was then supervised by the Ministry of Home Affairs to enable its transition into an Imperial Institute of Infectious Disease, which was later transferred to the Ministry of Education and finally incorporated into the Tokyo Imperial University as the Institute for Infectious Disease (IID) in 1914. Despite the frequent change of its name and jurisdiction, the institute had consistently played a central role in infectious disease research in our country.

Half of the faculty members of IID were recruited for the establishment of NIH. The new institute initially included 3 departments (research department, quality control department, and pilot production department) and an administration section, which shared the facilities with IID. In 1950s, to comply with the organizational regulation of the Ministry of Health and Welfare, NIH was expanded to 12 research departments, including bacteriology, virology/rickettsiology, tuberculosis, sero-immunology, and antibacterial substances. In 1955, NIH moved to the site of closed Naval Staff College, Kamiosaki, Shinagawa-ku, Tokyo (Shinagawa Labora-tories). Meanwhile, IID, which remained and devel-oped independently at the original site, was reorganized as the Institute of Medical Science of the University of Tokyo in 1967.

To cope with the large-scale epidemic of poliomyelitis, occurring in 1958, new facilities for test production and national test for lot release of poliomyelitis vaccines were urgently needed, and laboratories for quality control of vaccines were established in Musashi Murayama-shi in 1961 (Murayama Branch Laboratories). Thereafter, the Central Virus Diagnostic Laboratory and the Department of Measles Virus were established within the Murayama Branch Laboratories in 1963 and 1965, respectively. In 1981, a maximum containment (physical containment level 4: P4, also known as biosafety level 4: BSL4) laboratory was built as the world's fifth P4 facility. However, the facility was not operated as a P4 laboratory based on the request of the local community.

In 1978, the Tsukuba Primate Center for Medical Science was established as a branch of the Institute to provide monkeys of homogeneous quality necessary for national test for lot release and research work.

On the basis of the report dealing with the ideal status of the National Institute of Health (August 25, 1984), the whole Institute was reorganized after due consideration on separation of the research section from the quality control section. In 1992, the Shinagawa Laboratories were moved to the present site, Toyama, Sinjuku-ku, Tokyo (Toyama Research Laboratories). The quality control sections (vaccines and blood products) were concentrated to the Murayama Branch Laboratories. In the meanwhile, the AIDS Research Center was established in 1988 to deal with AIDS problems as an emerging infection.

In January 1997, the National Institute of Leprosy Research became a Branch of this Institute and started again its functions as the Leprosy Research Center. The Institute was renamed the National Institute of Infectious Diseases to show off more clearly the objec-tives of its establishment in April of the same year. At the same time, the Department of Epidemiology was reorganized into the Infectious Disease Surveillance Center to collect all the information of incidents of in-fectious diseases in the same place for enabling rapid measures.

The National Institute of Infectious disease has been reorganized one part of the organization since April 2002. The reason is to strengthen study system, and to promote research studies and its substantiality. This object has been guided by the Ministry of Health, Labour and Welfare as consistency of important point preparation and rebuilding of research institute on the basis of general promotion of public welfare scietific research for 21st century. Laboratories of Cariology and Periodontology of the Department of Oral Science in NIID has been integrated into the National Institute of Public Health. The Bacteriology and Virology Laboratories in the National Institute of Public health has been integrated into the Infectious Disease Surveillance Center in NIID. The Department of Biomedical Food Research has been transferred to the National Institute of Health Sciences.

In April 2005, the Division of Genetic Resources, the Tsukuba Primate Center for Medical Science and the Laboratory of Animal Models of the Department of Veterinary Science have moved to National Institute of Biomedical Innovation. In October 2005, the Division of Molecular Genetics has been reorganized into the Pathogen Genomics Center to conduct extensive molecular research on genomes of pathogenic viruses and bacteria in humans.

In April 2007, the Division of Quality Assurance was founded to assure the reliability of the national tests on biological products and antibiotics, and to manage the standard materials for testing.

In April 2009, the Influenza Virus Research Center was founded to expand and promote research activities related to the influenza virus. Accordingly, the Depart-ment of Virology III was redefined as a department responsible for research on respiratory viral diseases other than influenza. Moreover, in the Leprosy Research Center, the Departments of Microbiology and Bioregulation were expanded and integrated into a single department; the Department of Infection Control. It will develop efficient system for conducting fundamental and applied leprosy research and mycobacteriology.

In April 2013, the Department of Chemotherapy and Mycosis was renamed the Department of Mycology in order to strengthen mycological studies. The Infectious Disease Surveillance Center was renamed the Infectious Diseases Surveillance Center, to intensify epidemiological functions.

In April 2014, the Division of Quality Assurance and the Division of Radiological Protection and Biology were integrated into a single department; the Department of Quality Assurance and Radiological Protection, consisting of Laboratory of Quality Assurance and Laboratory of Radiological Production. This union is accompanied by introduction of review of summary protocols in October 2012 and reinforcement of international cooperation regarding quality assurance of biological products.

In August 2015, the BSL4 facility in Murayama Branch was designated by the Minister of Health, Labour and Welfare as the first BSL4 facility in Japan to possess class 1 pathogens under the Infectious Diseases Control Law.

In April 2017, the Antimicrobial Resistance Research Center (AMR-RC) was established with the aim to strengthen Japan Nosocomial Infection Surveillance (JANIS) and function as a comprehensive AMR think tank. Accordingly, the Department of Bacteriology II transferred research functions for nosocomial infectious diseases and antimicrobial resistance and quality assurance functions of antibiotics to AMR-RC. Hereafter the Department of Bacteriology II specialized in respiratory bacterial infectious diseases and toxigenic bacterial infectious diseases.

In April 2018, the 8th laboratory was established in addition to existing seven laboratories in AMR-RC.

In July 2019, NIID received a designation and permission from the Minister of Health, Labour and Welfare to import class 1 pathogens from overseas institutes under the Infectious Diseases Control Law. In September, NIID imported and possessed those pathogens in the BSL-4 facility in Murayama Branch.

In April 2020, the Division of Biosafety Control and Research and the Division of Experimental Animal Research were integrated as the Management Department of Biosafety and Laboratory Animal Research.

In addition, the Center for Emergency Preparedness and Response was established to play a central role in the emergency management of infectious disease events by delineating the offices responsible for crisis management, pathogen diagnosis, and laboratory trainings from the Infectious Disease Surveillance Center.

Division of Information System, which is responsible for the construction, operation and management of the institutewide network system, was added to the Department of Quality Assurance, Radiation Safety, and Information System (formerly the Department of Quality Assurance and Radiological Protection).

In April 2021, the following organizational restructuring was carried out in order to strengthen the crisis management system in light of the worldwide spread of COVID-19.

To strengthen and focus on research on acute respiratory viral infectious diseases including influenza, the Influenza Virus Research Center was reorganized as Research Center for Influenza and Respiratory Viruses.

The Department of Immunology was reorganized as the Research Center for Drug and Vaccine Development for promoting research and development.

In addition to the three existing laboratories in the Department of Virology III, some of the functions of the fourth laboratory were transferred to Research Center for Influenza and Respiratory Viruses, and the newly established fourth and fifth laboratories were added to strengthen the laboratory functions for lot release tests of vaccines.

In the Management Department of Biosafety and Laboratory Animal Research (the present name is “The Management Department of Biosafety, Laboratory Animal, and Pathogen Bank”), the existing two laboratories were divided into four laboratories, and the fifth through seventh laboratories responsible for the pathogen bank affairs were established.

Planning and Coordination became the Research Planning and Coordination Center in April 2021 so that the functions of inter-sectional coordination within the NIID as well as collaboration with other research institutions could be strengthened. The new Center has two offices.

The Center for Surveillance, Immunization, and Epidemiologic Research established eight new units in addition to the existing six units.

The Center for Emergency Preparedness and Response established another three offices in addition to the existing five offices.

The Center for Field Epidemic Intelligence, Research, and Professional Development (CFEIR) was established in April 2021 for strengthening field epidemiological investigation in collaboration with local governments and the Ministry of Health, Labour and Welfare, and for conducting both public health research and training in field epidemiology.

In April 2022, the department of Safety Research on Blood and Biological Products was reorganaized into the Research Center for Biological Products in the Next Generation and was established another laboratory in addition to the existing four laboratories.

In Department of Veterinary Science, a new fourth laboratory was established in addition to the current three laboratories.

In Pathogen Genomics Center, a new fourth laboratory was established in addition to the current three laboratories.

Functions

The Institute aims at carrying out extensive and original research projects on a variety of contagious diseases from the standpoint of preventive medicine, improving human health and welfare by suppressing infectious diseases, and clarifying and supporting the scientific background of health and medical admini-stration of the government. These functions may be summarized into ①research activities, ②reference services for infectious diseases, ③surveillance of infectious diseases, ④national control tests and other tests, ⑤international cooperation, and ⑥training activities.

1. Basic and applied research on infectious diseases

   Basic and applied research projects on infectious and other intractable diseases associated with the immune systems are under way. Particularly, molecular biological analyses of the etiological agents as well as development and application of rapid diagnostic methods and vaccines for important diseases emerging or re-emerging and also other traditional diseases are the main projects. Research on development of recombinant and other new concept-based vaccines (e.g., mucomembranous and DNA vaccines) are being worked out actively. In recent years, the environment surrounding infectious diseases has been changing dramatically; the increase in inbound tourists accompanied with development of international transport networks, the influence of criminal changes and global warming, and a glowing number of zoonosis and infections caused by antimicrobial resistance microbes are given as important issues. Thus, NIID has been developing multiple strategies to address emerging infectious disease threats in a wide range.

2. Reference services for infectious diseases

   The reference services include all that are necessary for ensuring the assay systems for infectious diseases. In concrete terms, the services involve storing and supplying pathogenic agents (pathogenic microorganisms and their products, parasites, and vector insects), standardizing the reagents, preparing and supplying reference materials needed for diagnosis and surveillance of infectious diseases, educating professional technicians, and information exchange. To carry on infectious disease reference services, a reference committee was organized, and in cooperation with prefectural public health institutes, a collaborative activities are carried out to control infectious diseases.

3. Infectious disease surveillance program, and collection, analysis, and feedback and distribution of information on infectious diseases

   As a national project of surveillance, This Institute collects reports of detection of infectious agents from prefectural public health institutes and those of incidents of infectious diseases from sentinel clinics in the whole country, based on the Infectious Diseases Control Law. This information is accessible to the public, as weekly (IDWR) and monthly (IASR) reports. In case of occurrence of an epidemic or outbreak of an infectious disease, epidemiological investigations will be carried out and the information exchanged with infectious disease surveillance organizations in other countries. Field Epidemiology Training Program, Japan (FETP-J) provides a training course of field epidemiologists, who enable to conduct effective epidemiological investigations. To make these activities more efficient, the Infectious Disease Surveillance Center organized in April 1997, and was renamed the Infectious Diseases Surveillance Center, to intensify epidemiological functions in April, 2013. This Center is responsible for surveillance on all of targeted diseases by Infectious Disease Control Law.

4. National lot release and other tests, and research on quality control of biological products and antibiotics
   1. Biological products (various vaccines and blood products, etc.) for prevention, treatment and diagnosis of infectious diseases and other specific diseases are being subjected to national lot release for securing the quality, efficacy and safety. Although judgement on national lot release had been made exclusively by the test results performed by NIID since long ago, review of the summary protocol was introduced to national lot release for vaccines and other products in October 2012 and July 2021, respectively.
   2. In addition to administratively required tests, tests requested by clients are being carried out for biological products and antibiotics.
   3. Standards, reference materials, etc. for such biological products and antibiotics necessary for national lot release and other tests are being produced. Besides, research on quality control of biological products and antibiotics such as development of new test methods and improvement of test methods are being conducted based on the latest information and knowledge.
5. International cooperation activities

   To prepare for emerging and re-emerging infectious diseases as global threats to the public health, NIID engages in various international activities including dissemination of information on a global scale, contribution on research collaboration and technology transfer while cooperating with World Health Organization (WHO) and other foreign research institutes. Since 2003, NIID has exchanged the Memorandum of Understandings (MOUs) on research collaboration with its counterparts e.g. China, South Korea, Indonesia, Viet Nam, India, Mongolia, Thailand, Taiwan, etc. Additionally, NIID annually organizes multilateral international meetings such as Japan China-Korea Forum on Infectious Diseases Control and Prevention, and properly advances bilateral collaborative research activities.

   WHO-designated centres and WHO reference laboratories

   • Japanese Encephalitis Global Specialized Laboratory (Department of Virology I)
   • Collaborating Centre for Virus Reference and Research (Enterovirus) (Department of Virology II)
   • Polio Global Specialized Laboratory (Department of Virology II)
   • Polio Regional Reference Laboratory (Department of Virology II)
   • Measles and Rubella Global Specialized Laboratory (Department of Virology III)
   • Measles and Rubella Regional Reference Laboratory (Department of Virology III)
   • WHO Collaborating Centre for Reference and Research on Influenza (Research Center for Influenza and Respiratory Viruses)
   • WHO National Influenza Centre (Research Center for Influenza and Respiratory Viruses)
   • H5 Influenza Reference Laboratory (Research Center for Influenza and Respiratory Viruses)
   • Essential Regulatory Laboratory (Research Center for Influenza and Respiratory Viruses)
   • Collaborating Centre on Standardization and Evaluation of Biologicals (Department of Quality Assurance, Radiation Safety, and Information System)
   • Human Papillomavirus Laboratory Network Western Pacific Regional Reference Laboratory (Pathogen Genomics Center)
   • WHO Collaborating Centre for AMR Surveillance and Research (Antimicrobial Resistance Research Center)
   • Reference Laboratory for WHO Global Surveillance of Drug Resistance in Leprosy (Leprosy Research Center)

    

6. Training programs

   Various kinds of group and individual technical trainings on AIDS, poliomyelitis, and leprosy are being given to foreign trainees. In addition, NIID plans and conducts training programs for the workers from domestic research organizations including public health institutes.

7. Public communication

   The Institute facilitates outreach activities such as NIID Open Day at both Toyama and Murayama Research Laboratories that engage the public in our missions and research goals.