Albert Cheung Hoi Yu, Ph.D. Professor Infectious Disease Center, Peking University Professor and Vice-director Neuroscience Research Institute, Peking University Chairman and CEO Hai Kang Life Corporation Limited Beijing Hai Kang DNA Chips

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Albert Cheung Hoi Yu, Ph.D.ProfessorInfectious
Disease Center, Peking UniversityProfessor and
Vice-directorNeuroscience Research Institute,
Peking UniversityChairman and CEO Hai Kang
Life Corporation LimitedBeijing Hai Kang DNA
Chips Limitedachy_at_hsc.pku.edu.cn
Collaborative Opportunities on Bioinformatics in
the Diagnosis of Infectious Diseases Our
Preparedness in Battle Against Avian Influenza?
2nd ASEAN China International Bioinformatics
Workshop, April 2008
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Avian Influenza (AI) A Global Threat !
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Influenza Pandemic Preparedness Plan

• ? Surveillancein man animals
• ? Stockpiling and logistics
• ? Emergency responses
• ? Public health
• ? Community
• ? Public communication
• ? Coordination and command

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Phases of Alert
WHO
China
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Strategy of AI Control In China
National Ministry of Public Health With
Provincial Departments of Health, Local Health
Bureaus
3. Reporting of confirmed diagnostic result
4.Communication, feedbacks proposed response
National CDC
National Medical Expert Team
2. Reporting / Delivery of sample for diagnosis
confirmation
Provincial Medical Expert Team
Provincial CDC
Cooperation Diagnosis and Treatment

1. Reporting of suspected cases

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Surveillance of AI in Animals

• During outbreak
• Detection and report of infection by farmers and
  volunteer, based on clinical criteria (5 deaths
  in flock), to activate pre-emptive culling,
  confirmed by lab. (cloacal swab viral
  isolation)
• After outbreak
• Maintenance of clinical-based surveillance with
  lab. testing to confirm freedom from disease in
  control zone around infected area for 21 days,
  then 5 months (OIE)
• Proactive countrywide community survey to detect
  and destroy infected flocks, then twice a year

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Surveillance of AI in Humans

• Detection and report of all pneumonia flu-like
  illnesses with history of exposure to sick/dead
  poultry or of contact with pneumonia cases
• Nasopharyngeal swab of all cases sent for rapid
  flu test, and conventional test for H5N1.
• Investigations of all reported cases by trained
  epidemiology teams.
• Daily situation monitoring, daily update on
  website .

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Pandemic Planning Diagnostic Pyramid
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AIV Family Tree
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Evolving Viruses

• H5N1 viruses in 1997, 2003, 2004 and 2005 are
  genetically and antigenically different
• Different virus clades encountered in countries
  of the region
• Clade 1 (Lao, Thailand, Vietnam, Cambodia,
  China)
• Clade 2-subclade 3 (China, Thailand, Cambodia,
  Vietnam)
• Clade 2-subclade 1 (Indonesia)
• Sequence variation should be considered in
  diagnostic development

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The Battle Against Infectious Disease
To defeat an infectious disease, you must control
its transmission from infected people to healthy
ones. The critical issues are planning,
surveillance, and getting an early warning. It
was important to find ways to rapidly tell people
that they are not infected.
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AI in China
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Outbreaks of AI in Poultry and Human Cases in
Thailand
Jun-April 2005
Jan-May 2004
May 2005- Dec 05
Source BOE, MOPH
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• Lab Conditions
• No temperature control nor heating temp in lab
  was about 10oC
• Walls and floors did not have appropriate
  covering (tiles and bumpy lino)
• Electricity supply not guaranteed (no generator)
  interruptions experienced during testing
• No freezer below about 8oC

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Challenges for Diagnostics from Global Public
Health Perspective As accurate as necessary
to ensure WHO's public health responsibilities
fulfilled As quick as possible to detect the
emergence of new variants of human pandemic
potential to trigger outbreak response,
investigation and rapid containment whenever
needed As simple as possible the majority of
diagnostic labs in the world does not have
advanced lab settings many crucial diagnosis
conducted under huge pressure
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• Symptoms
• Respiratory distress syndrome
• X-ray evidence of lung damage
• Fever

Current Detection Methods Ag / Ab-based
method Microbiological evidence of virus (virus
isolation) Conventional PCR Real
time-PCR NASBA New Method Modified Enhanced real
time-PCR

• Users
• Where?
• Who? User-friendly?
• Affordable?

Infection
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Amplification Technology of NASBA
Isothermal amplification technique ? comparable
results within different test units Simplified
operation process ? reduced contamination, higher
reproducibility
PCRs false positive result
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NASBA Protocol
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NASBA System
Adapt to regular instrument
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Participation of NASBA-EOC Detection in
theInfluenza Surveillance Program Commissioned
by the National AIV Task Force

• NASBA-EOC Takes part in the project implemented
  by National AIV task force
• Surveillance of avian influenza virus (generic
  and subtype H5), human influenza virus,
  parainfluenza virus, and other selective
  pneumonia-causing pathogens in Beijing population
• Beijing Hai Kang DNA Chips Limited provides NASBA
  AIV / H5 test kits for the surveillance program

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National Task Force for Human AIV
Training on AIV diagnosis using the NASBA EOC
method to the National AIV task force members in
Beijing, China
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Multiplex NASBA!
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Molecular Pneumonia Detection Systems

• Project awarded by the China Ministry of Science
  and Technology (a 863 project)
• We collaborated various hospitals in Beijing
  including hospitals affiliated Peking University,
  Chao Yang Hospital, You An Hospital and Di Tan
  Hospital of Capital Medical University
• Development of multiplex NASBA, ERT-PCR and other
  detection system/ technology for various
  pneumonia-causing pathogens (including SARS, AIV,
  influenza, etc.)
• Development of a Lab-On-A-Chip (LOAC) system

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Was it possible to establish rapid and accurate
tests for Infectious diseases in an outbreak
situation?
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Difficulties in Getting Good Diagnostic Kit
Validated!

• Adequate clinical samples
• Well characterized samples are indispensable for
  the development and evaluation of diagnostic test
• Appropriate and adequate specimens
• Good quality
• Adequate clinical information
• Appropriate labeling and storage
• Good data management

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Development of Sustainable and Integrated
Management System

• Development of knowledge management mechanism
  during the inter pandemic period
• Development of knowledge management mechanism
  during pandemic
• Establishment of a system for coordination and
  communication among various organizations during
  pandemic
• Coordination with foreign and international
  organizations
• 5. Monitoring and evaluation

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Major success factors for AI control

• ? Strong leadership and support of the Government
• ? Close co-operation between public health and
  animal health authorities, and among partners in
  multi sectors
• ? Proactive risk communication to the public and
  strong public involvement
• ? Extensive international collaborations,
  especially with WHO, OIE, FAO, APEC,ASEAN-China-Ko
  rea-Japan,
• ? Existing infrastructure (surveillance,
  laboratories,
• disease control, hospital infection, trained
  personnel)

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The influenza epidemic of 1918 killed 20 million
in just 18 months. With 25 million Americans
alone infected during the influenza epidemic, it
was hard to provide care for everyone. The Red
Cross, seen here with masks over the faces of the
nurses, often worked around the clock. Source
Courtesy of the National Library Museum.
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ThankYou!
??!
CNN - Businesses brace for pandemic 3 November
2005