Transcript ウイルス感染症の撲滅の恩恵と問題点 - The National Academies of

Highly containment laboratory in the
National Institute of Infectious Diseases,
Tokyo, Japan: activities, circumstances,
and future challenges
Masayuki Saijo, M.D., Ph. D
Department of Virology 1,
National Institute of Infectious Diseases
Current situation of BSL-4
facilities in NIID
• Glove box-type BSL-4 facility was constructed and installed in the
NIID (Murayama annex) in early 1980’s.
• Role of the Special Pathogens Laboratory in Dept Virol 1, NIID
– Basic science for viral hemorrhagic fevers and other emerging
virus infections
– Quality Control of Smallpox vaccine
– Preparedness for the risk of viral
• The BSL-4 facility has not yet operated as BSL-4 facility but as BSL3 laboratories.
– Opposition by the residents and local municipality to the
operation of the facility as BSL-4
Japanese Infectious Control Law
• Ebolavirus, Marburg virus, Crimean-Congo
hemorrhagic fever virus, Lassa virus, South
American hemorrhagic fever viruses, Variola
virus, and Yersinia pestis are defined as BSL-4
pathogens in the JIDC law.
• The law restricts importation, possession,
transportation, transfer and sterilization.
• Furthermore, the law tightened the control of
animal importation.
Research Activities in Highly
Containment Laboratory
• Development of diagnostic systems for Hemorrhagic fever
viruses (Ebola, Marburg, CCHF, Lassa, etc) -mission
• Monkeypox virus infections
– Pathogenesis, diagnostics, immunology
• SARS
– Diagnostics, Vaccine development, Animal model development, and
Pathogenesis
• Efficacy assessment of a newly developed highly
pathogenic avian influenza vaccine using nonhuman
primate models
• Efficacy assessment of a highly attenuated smallpox vaccine,
LC16m8, using nonhuman primate models
– Induction of protective efficacy, Post-exposure vaccination, long-term
efficacy
Recombinant NP-based diagnosis
of CCHF
Tang Q, et al. A patient with Crimean-Congo
hemorrhagic fever diagnosed with recombinant
nucleoprotein-based antibody detection systems.
Clin Diag Lab Immunol 10:489-491, 2003
Clinical course
Patient: 28-year old shepherd in the Xinjiang Uygur
Autonomous Region in 2001
Symptoms：
fever, unconsciousness, hemorrhage (nostril,
gingiva, rectum)
Laboratory findings：
anemia (Hb 10.0 g/dl), thrombocytopenia
(8.41010/L), elevated transaminases (ALT, AST,
LDH;173, 216, 268 U/L), hyperbilirubinamia,
hypoalbuminamia
Virological test results on CCHF virus infection
Days from onset
(Days)
1
5
9
RT-PCR (nested)
Ag-capture ELISA
(OD405)
+
0.381 0.007 0.000
IgG-ELISA (1:100)
(OD405) (1:400)
0.075 0.924 1.882
0.031 0.486 0.972
IgM-capture ELISA
(OD405) (1:100)
(1:400)
0.020 2.692 2.711
0.040 1.606 2.001
1
300
200
5
9 NC
International collaborations
• US CDC (Atlanta, GA)
– Ebola, Marburg, Smallpox (vaccine study)
• INSERM (Lyon, France)
– Lassa, Marburg
• China CDC (Beijing, China)
– Crimean-Congo hemorrhagic fever
• RITM (Manila, the Philippines)
– Reston Ebolavirus
• University of Maiduguri (Maiduguri, Nigeria)
– Hemorrhagic fevers
• University of Ghana (Acura, Ghana)
– Hemorrhagic fevers
Future challenges
-key player• Need to operate the facility as BSL-4
laboratory in order to prepare the possible
outbreak of highly pathogenic hemorrhagic
fever virus infections and other novel
emerging infections not only in Japan, but
also in the other part of the world.
• Need to play an important role to combat
the highly pathogenic infections in
collaboration with the key partners in the
world.
Future challenges
-operation• Requirement of mutual understandings on
the safety and operation risks between the
NIID and communities.
• Requirement of mutual collaboration to the
operation of BSL-4 facilities between NIID
and the Ministry of Health, Labor, and
Welfare of Japan.
Action plans
• Mutual understanding
– Periodical seminars on infections diseases to
the residents in communities
– Establishment of Safety committee between
the local municipalities and the NIID
– Others
• Mutual collaboration
– Between the NIID and MHLW
– Between the NIID and Ministry of Education,
Culture, Science, and Technology
– Between the NIID and Academics