Highly%20containment%20laboratory%20in%20the%20National%20Institute%20of%20Infectious%20Diseases,%20Tokyo,%20Japan:%20activities,%20circumstances,%20and%20future%20challenges

1
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

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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
  1980s.
• 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 BSL-3 laboratories.
• Opposition by the residents and local
  municipality to the operation of the facility as
  BSL-4

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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.

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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

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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 10489-491, 2003

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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,
  LDH173, 216, 268 U/L), hyperbilirubinamia,
  hypoalbuminamia

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Virological test results on CCHF virus infection
Days from onset 1 5 9 (Days) RT-PCR
(nested) - - Ag-capture ELISA 0.381 0.007 0.00
0 (OD405) IgG-ELISA (1100) 0.075 0.924 1.882 (O
D405) (1400) 0.031 0.486 0.972 IgM-capture
ELISA (OD405) (1100) 0.020 2.692 2.711
(1400) 0.040 1.606 2.001
1
5
9
NC
300
200
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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

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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.

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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.

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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