- Email: [email protected]
Institute Profile: National Institute of Infectious Diseases
512
Forum
TRENDS in Microbiology Vol.9 No.10 October 2001
Science and Society
Institute Profile: National Institute of Infectious Diseases Hiroshi Yoshikura and Takeshi Kurata A profile of the the National Institute of Infectious Diseases (NIID) at Toyama Shinjuku-Ku, Tokyo, Japan.
The National Institute of Infectious Diseases (NIID; Fig. 1), formerly known as the National Institute of Health (NIH), was founded in 1947 by the Ministry of Health and Welfare. At this time, Japan required a central institute to conduct research and investigate vaccine control that would contribute to the improvement of national health and welfare. After World War 2, epidemic and endemic diseases were widespread throughout the country and it was essential to restore sanitary conditions as quickly as possible. Research at the NIID therefore concentrated on communicable diseases, including their etiology, immunology, epidemiology, prophylaxis and therapy, and on assays of biological products and antibiotics. Today, the NIID also has a strong relationship with the WHO, containing several WHO-cooperating centres (Box 1). Functions and responsibilities
At present, the NIID has various functions and responsibilities, which include conducting and coordinating research projects of national importance on the causative agents and pathogenesis of infectious diseases and their diagnosis, prevention and treatment. The Institute also functions as a national vaccine and blood-product control laboratory, conducting potency assays and safety tests as well as basic research concerning quality control for these products, and as a reference laboratory for the diagnosis of infectious diseases, storing and supplying pathogenic agents, standardizing reagents and preparing and supplying reference materials. The NIID also publishes the bimonthly Japanese Journal of Infectious Diseases. The NIID has an important role as an information centre for the surveillance of infectious disease agents not only in Japan but also worldwide, collecting, analyzing and distributing relevant laboratory information. This is carried out http://tim.trends.com
Fig. 1. The National Institute of Infectious Diseases (NIID) at Toyama Shinjuku-Ku, Tokyo.
in collaboration with other public health institutes, health centres and designated hospitals and provides information on infectious diseases to the nation. As a national surveillance centre, the NIID collects reports of incidents of infectious disease from public health institutes and sentinel clinics in the whole country, and this information is made accessible to the public. In the case of an epidemic or outbreak of an infectious disease, epidemiological investigations are carried out and the information is exchanged with infectious disease surveillance organizations in other countries. To make these activities more efficient, the Infectious Disease Surveillance Centre (IDSC), established in April 1997, serves as the coordinating centre. Departments and centres
The NIID is organized into 16 departments and four centres, each of which concentrates on specific aspects of infectious diseases and some of which are highlighted here. Virology departments
The Department of Virology 1 comprises five laboratories specializing in respiratory viruses, neurological viruses, herpesviruses, special pathogens, and Rickettsia and Chlamydia and is engaged in research, quality control of vaccines and reference activities. In the neurological virus lab, DNA vaccines to Japanese encephalitis (JE) and dengue viruses have been developed. These experimental vaccines induced high levels of neutralizing antibodies to their respective viruses and
protected mice from lethal challenge; the JE DNA vaccine is being examined for protective immunity in monkeys. In the special pathogens lab, antibody- or antigendetection diagnostic systems have been developed for viral haemorrhagic fevers, using recombinant nucleoproteins. Research in Department of Virology 2 is focused on the biological characterization and pathogenesis of diarrhoea viruses, enteroviruses, poxviruses, tumour viruses and hepatitis viruses, and the development of new vaccines and diagnostics for the viral diseases they cause. The enteroviruses section is involved in the WHO’s global polio eradication programme and has made a major contribution to the polio-free status of the Western Pacific region. The department also functions as a regional reference laboratory for the Western Pacific region. A recent interesting finding from this group was the detection of vaccine-derived neuropathogenic polioviruses in the environment. The hepatitis section contributed to the discovery of hepatitis C virus (HCV) and a major accomplishment of this group was to show that the HCV core protein is involved in hepatocarcinogenesis. The Department of Viral Diseases and Vaccine Control comprises six laboratories investigating poliomyelitis vaccines; measles virus and vaccines; mumps virus and vaccines; rubella virus and vaccines; hepatitis vaccines; and cytokines. As part of the National Control Laboratory, these labs are responsible for the quality control of vaccines and interferon products, as well as testing the potency of human immunoglobulin preparations. This department is also collaborating with the WHO by participating in the Expanded Programme on Immunization (EPI) for the global eradication of poliomyelitis and measles. The control of varicella, influenza, rabies and JE vaccines is also a focus of the department. Bacteriology departments
The Department of Bacteriology researches various aspects of host–bacteria interactions and gene regulation using
0966-842X/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S0966-842X(01)02202-8
Forum
TRENDS in Microbiology Vol.9 No.10 October 2001
Box 1. Centres assigned to the National Institute of Infectious Diseases WHO-designated centres Collaborating centre for the production of immunological products (Dept of Bacterial and Blood products) Collaborating centre for influenza (Dept of Virology 1) Collaborating centre for enteroviruses (Dept of Virology 2) Collaborating centre for Small Laboratory Animals (Division of Experimental Animal Research) International Union of Microbiological Societies (IUMS)-assigned centre Enteric phage-typing centre (Dept of Bacteriology) Other centres The following centres assigned by WHO are continuing research activities as the designated National Centre in Japan: Shigella/Salmonella Centre (Dept of Bacteriology) National Serum Reference Bank (Infectious Disease Surveillance Centre)
many pathogens including Shigella, Legionella, Salmonella, enterohaemorrhagic Escherichia coli and Borrelia. Some recent findings include: (1) the interaction of IpaC of Shigella with β-catenin in the cytoplasm of HeLa cells, resulting in phosphorylation and destabilization of the functional cadherin–catenin complex, thus possibly facilitating further bacterial invasion through the basolateral surface of the epithelial cell; (2) it was shown that in mice, NADPH oxidase activity is essential for the inhibition of pulmonary multiplication of Legionella pneumophila, and that the katA and katB but not sodC genes of Legionella are essential for its virulence; and (3) the fliZ mutation of Salmonella typhimurium reduced not only the amounts of secreted flagella proteins but also several secreted invasion proteins encoded by the genes within Salmonella pathogenicity island 1. This finding demonstrated that the gene regulation of flagella and invasion proteins is linked. These results are being applied to the development of diagnostic methods and preventive treatments. Research in the Department of Bacterial and Blood Products is concentrated on the control and prevention of bacterial infections including diphtheria, pertussis, tetanus, tuberculosis and botulism, and also focuses on national surveillance of nosocomial infections caused by drugresistant bacteria. The surveillance of antibiotic-resistant Gram-negative bacteria that produce so-called extended spectrum β-lactamases (ESBLs) or IMP-1 metallo-β-lactamases revealed the new http://tim.trends.com
ESBL and SHV-24 from a clinically isolated Escherichia coli. The isolation frequency of ESBL producers was estimated to be <1.0% whereas that of IMP-1 producers was shown to be ~4.4% in Serratia marcescens by PCR. Parasitology
The research objectives of the Department of Parasitology are directed toward understanding the biological features and pathogenesis of protozoan and helminthic parasites, including nematodes, trematodes and cestodes, with a view to their control and prevention. This department is responsible for the development of practical systems to detect contamination of drinking water and foods by enteric protozoa, such as Cryptosporidium. Research is also conducted into the relationships between host free-living amoebae and Legionella in man-made aquatic environments. The identification and characterization of unique cellular and biochemical events in the parasitic protozoa, including Plasmodium and Trypanosoma species, have also attracted the attention of department researchers interested in developing prophylactic, chemotherapeutic and diagnostic measures. A recently established research area is the analysis and improvement of antigens for the diagnosis of the lungfluke infection (paragonimiasis) using molecular technology. Research centres
The NIID also organizes its research efforts into centres dedicated to the understanding
513
and prevention of important human infectious diseases. The AIDS Research Centre was founded in April 1988 to reinforce and coordinate research activities related to HIV/AIDS. The centre has two major research groups and three research laboratories. Current topics under investigation include HIV vaccine development based on Mycobacterium bovis bacille Calmette–Guérin (BCG), parainfluenza and other vectors; molecular epidemiological studies in the Western Pacific and South East Asian regions; and the study of drug-resistant HIV arising during anti-HIV treatment. The IDSC was designated a new department in the NIID in 1997. Infectious disease surveillance in Japan is operated by the IDSC under the Infectious Disease Control Law enacted in April 1999. Data on infectious disease surveillance and information is disseminated by IDSC in various ways including our website (http://idsc.nih.go.jp/index-j.html), the Infectious Disease Weekly Report (IDWR) and publications such as the Infectious Agent Surveillance Report (IASR). The centre also provides training for local public health laboratory workers in standard microbiological techniques and hosts workshops on risk management of infectious diseases for medical doctors working in the field of public health. Finally, the IDSC serves as a think-tank for infectious disease control policies. The Leprosy Research Centre deals with leprosy and other mycobacterial infections. This centre is organized into two departments, the Department of Microbiology and the Department of Bioregulations. Finally, the Tsukuba Primate Centre for Medical Science (TPC) was founded to raise and rear non-human primates free from major zoonotic infectious diseases. About 200 cynomolgus monkeys are supplied annually not only for safety tests of live vaccines but also for biomedical studies including microbiology, immunology, AIDS research and gene therapy. For a complete list of the current NIID research activities, see http://www.nih.go.jp Hiroshi Yoshikura Takeshi Kurata* National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-Ku, Tokyo 162-8640, Japan. *e-mail: [email protected]
Forum
TRENDS in Microbiology Vol.9 No.10 October 2001
Science and Society
Institute Profile: National Institute of Infectious Diseases Hiroshi Yoshikura and Takeshi Kurata A profile of the the National Institute of Infectious Diseases (NIID) at Toyama Shinjuku-Ku, Tokyo, Japan.
The National Institute of Infectious Diseases (NIID; Fig. 1), formerly known as the National Institute of Health (NIH), was founded in 1947 by the Ministry of Health and Welfare. At this time, Japan required a central institute to conduct research and investigate vaccine control that would contribute to the improvement of national health and welfare. After World War 2, epidemic and endemic diseases were widespread throughout the country and it was essential to restore sanitary conditions as quickly as possible. Research at the NIID therefore concentrated on communicable diseases, including their etiology, immunology, epidemiology, prophylaxis and therapy, and on assays of biological products and antibiotics. Today, the NIID also has a strong relationship with the WHO, containing several WHO-cooperating centres (Box 1). Functions and responsibilities
At present, the NIID has various functions and responsibilities, which include conducting and coordinating research projects of national importance on the causative agents and pathogenesis of infectious diseases and their diagnosis, prevention and treatment. The Institute also functions as a national vaccine and blood-product control laboratory, conducting potency assays and safety tests as well as basic research concerning quality control for these products, and as a reference laboratory for the diagnosis of infectious diseases, storing and supplying pathogenic agents, standardizing reagents and preparing and supplying reference materials. The NIID also publishes the bimonthly Japanese Journal of Infectious Diseases. The NIID has an important role as an information centre for the surveillance of infectious disease agents not only in Japan but also worldwide, collecting, analyzing and distributing relevant laboratory information. This is carried out http://tim.trends.com
Fig. 1. The National Institute of Infectious Diseases (NIID) at Toyama Shinjuku-Ku, Tokyo.
in collaboration with other public health institutes, health centres and designated hospitals and provides information on infectious diseases to the nation. As a national surveillance centre, the NIID collects reports of incidents of infectious disease from public health institutes and sentinel clinics in the whole country, and this information is made accessible to the public. In the case of an epidemic or outbreak of an infectious disease, epidemiological investigations are carried out and the information is exchanged with infectious disease surveillance organizations in other countries. To make these activities more efficient, the Infectious Disease Surveillance Centre (IDSC), established in April 1997, serves as the coordinating centre. Departments and centres
The NIID is organized into 16 departments and four centres, each of which concentrates on specific aspects of infectious diseases and some of which are highlighted here. Virology departments
The Department of Virology 1 comprises five laboratories specializing in respiratory viruses, neurological viruses, herpesviruses, special pathogens, and Rickettsia and Chlamydia and is engaged in research, quality control of vaccines and reference activities. In the neurological virus lab, DNA vaccines to Japanese encephalitis (JE) and dengue viruses have been developed. These experimental vaccines induced high levels of neutralizing antibodies to their respective viruses and
protected mice from lethal challenge; the JE DNA vaccine is being examined for protective immunity in monkeys. In the special pathogens lab, antibody- or antigendetection diagnostic systems have been developed for viral haemorrhagic fevers, using recombinant nucleoproteins. Research in Department of Virology 2 is focused on the biological characterization and pathogenesis of diarrhoea viruses, enteroviruses, poxviruses, tumour viruses and hepatitis viruses, and the development of new vaccines and diagnostics for the viral diseases they cause. The enteroviruses section is involved in the WHO’s global polio eradication programme and has made a major contribution to the polio-free status of the Western Pacific region. The department also functions as a regional reference laboratory for the Western Pacific region. A recent interesting finding from this group was the detection of vaccine-derived neuropathogenic polioviruses in the environment. The hepatitis section contributed to the discovery of hepatitis C virus (HCV) and a major accomplishment of this group was to show that the HCV core protein is involved in hepatocarcinogenesis. The Department of Viral Diseases and Vaccine Control comprises six laboratories investigating poliomyelitis vaccines; measles virus and vaccines; mumps virus and vaccines; rubella virus and vaccines; hepatitis vaccines; and cytokines. As part of the National Control Laboratory, these labs are responsible for the quality control of vaccines and interferon products, as well as testing the potency of human immunoglobulin preparations. This department is also collaborating with the WHO by participating in the Expanded Programme on Immunization (EPI) for the global eradication of poliomyelitis and measles. The control of varicella, influenza, rabies and JE vaccines is also a focus of the department. Bacteriology departments
The Department of Bacteriology researches various aspects of host–bacteria interactions and gene regulation using
0966-842X/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S0966-842X(01)02202-8
Forum
TRENDS in Microbiology Vol.9 No.10 October 2001
Box 1. Centres assigned to the National Institute of Infectious Diseases WHO-designated centres Collaborating centre for the production of immunological products (Dept of Bacterial and Blood products) Collaborating centre for influenza (Dept of Virology 1) Collaborating centre for enteroviruses (Dept of Virology 2) Collaborating centre for Small Laboratory Animals (Division of Experimental Animal Research) International Union of Microbiological Societies (IUMS)-assigned centre Enteric phage-typing centre (Dept of Bacteriology) Other centres The following centres assigned by WHO are continuing research activities as the designated National Centre in Japan: Shigella/Salmonella Centre (Dept of Bacteriology) National Serum Reference Bank (Infectious Disease Surveillance Centre)
many pathogens including Shigella, Legionella, Salmonella, enterohaemorrhagic Escherichia coli and Borrelia. Some recent findings include: (1) the interaction of IpaC of Shigella with β-catenin in the cytoplasm of HeLa cells, resulting in phosphorylation and destabilization of the functional cadherin–catenin complex, thus possibly facilitating further bacterial invasion through the basolateral surface of the epithelial cell; (2) it was shown that in mice, NADPH oxidase activity is essential for the inhibition of pulmonary multiplication of Legionella pneumophila, and that the katA and katB but not sodC genes of Legionella are essential for its virulence; and (3) the fliZ mutation of Salmonella typhimurium reduced not only the amounts of secreted flagella proteins but also several secreted invasion proteins encoded by the genes within Salmonella pathogenicity island 1. This finding demonstrated that the gene regulation of flagella and invasion proteins is linked. These results are being applied to the development of diagnostic methods and preventive treatments. Research in the Department of Bacterial and Blood Products is concentrated on the control and prevention of bacterial infections including diphtheria, pertussis, tetanus, tuberculosis and botulism, and also focuses on national surveillance of nosocomial infections caused by drugresistant bacteria. The surveillance of antibiotic-resistant Gram-negative bacteria that produce so-called extended spectrum β-lactamases (ESBLs) or IMP-1 metallo-β-lactamases revealed the new http://tim.trends.com
ESBL and SHV-24 from a clinically isolated Escherichia coli. The isolation frequency of ESBL producers was estimated to be <1.0% whereas that of IMP-1 producers was shown to be ~4.4% in Serratia marcescens by PCR. Parasitology
The research objectives of the Department of Parasitology are directed toward understanding the biological features and pathogenesis of protozoan and helminthic parasites, including nematodes, trematodes and cestodes, with a view to their control and prevention. This department is responsible for the development of practical systems to detect contamination of drinking water and foods by enteric protozoa, such as Cryptosporidium. Research is also conducted into the relationships between host free-living amoebae and Legionella in man-made aquatic environments. The identification and characterization of unique cellular and biochemical events in the parasitic protozoa, including Plasmodium and Trypanosoma species, have also attracted the attention of department researchers interested in developing prophylactic, chemotherapeutic and diagnostic measures. A recently established research area is the analysis and improvement of antigens for the diagnosis of the lungfluke infection (paragonimiasis) using molecular technology. Research centres
The NIID also organizes its research efforts into centres dedicated to the understanding
513
and prevention of important human infectious diseases. The AIDS Research Centre was founded in April 1988 to reinforce and coordinate research activities related to HIV/AIDS. The centre has two major research groups and three research laboratories. Current topics under investigation include HIV vaccine development based on Mycobacterium bovis bacille Calmette–Guérin (BCG), parainfluenza and other vectors; molecular epidemiological studies in the Western Pacific and South East Asian regions; and the study of drug-resistant HIV arising during anti-HIV treatment. The IDSC was designated a new department in the NIID in 1997. Infectious disease surveillance in Japan is operated by the IDSC under the Infectious Disease Control Law enacted in April 1999. Data on infectious disease surveillance and information is disseminated by IDSC in various ways including our website (http://idsc.nih.go.jp/index-j.html), the Infectious Disease Weekly Report (IDWR) and publications such as the Infectious Agent Surveillance Report (IASR). The centre also provides training for local public health laboratory workers in standard microbiological techniques and hosts workshops on risk management of infectious diseases for medical doctors working in the field of public health. Finally, the IDSC serves as a think-tank for infectious disease control policies. The Leprosy Research Centre deals with leprosy and other mycobacterial infections. This centre is organized into two departments, the Department of Microbiology and the Department of Bioregulations. Finally, the Tsukuba Primate Centre for Medical Science (TPC) was founded to raise and rear non-human primates free from major zoonotic infectious diseases. About 200 cynomolgus monkeys are supplied annually not only for safety tests of live vaccines but also for biomedical studies including microbiology, immunology, AIDS research and gene therapy. For a complete list of the current NIID research activities, see http://www.nih.go.jp Hiroshi Yoshikura Takeshi Kurata* National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-Ku, Tokyo 162-8640, Japan. *e-mail: [email protected]