Bioterrorism by pengtt

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									H5N1 and XDR-TB Update
          Steven Lawrence, MD, MSc
Associate Director-Emergency Response Planning, MRCE
             Division of Infectious Diseases
       Washington University School of Medicine


         PandemicPrep.Org Quarterly Meeting
               September 12th, 2007
Disclosure Statement


  No Conflicts of Interest
H5N1 Avian Influenza Update
 Geographic spread continues
 New data on pandemic risk
 Antiviral update
       Stockpile
       Resistance
   Vaccine update
       Stockpile
       Candidates
   Non-pharmaceutical interventions
Update from DHHS
   "Everything we do before a pandemic will
    seem alarmist. Everything we do after a
    pandemic will seem inadequate."
             DHHS Secretary Leavitt 6/13/07


   Recommended public messages
        Stockpile food, water, meds, supplies
        Proper hand hygiene and cough etiquette
        Stay home when possible


    http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jun1407summit.html
H5N1 (as of 9/10/07)




                  http://www.pandemicflu.gov/
    H5N1 Human Cases – 9/10/07
                  2003            2004            2005            2006             2007            Total
 Country
             case   death    case   death    case   death    case   death     case   death    cases   death

Azerbaijan    0          0    0          0    0          0    8          5     0          0    8           5
Cambodia      0          0    0          0    4          4    2          2     1          1    7           7
  China       1          1    0          0    8          5   13          8     3          2    25      16
 Djibouti     0          0    0          0    0          0    1          0     0          0    1           0
  Egypt       0          0    0          0    0          0   18          10   20          5    38      15
Indonesia     0          0    0          0   20      13      55          45   31      27      106      85
   Iraq       0          0    0          0    0          0    3          2     0          0    3           2
  Laos        0          0    0          0    0          0    0          0     2          2    2           2
 Nigeria      0          0    0          0    0          0    0          0     1          1    1           1
Thailand      0          0   17      12       5          2    3          3     0          0    25      17
 Turkey       0          0    0          0    0          0   12          4     0          0    12          4
Viet Nam      3          3   29      20      61      19       0          0     7          4   100      46
  Total       4          4   46      32      98      43      115         79   65      42      328      200
 Warning Shot Fired
 •   Virginia turkey flock H5N1
      –   Apparently healthy
      –   Antibody test, routine pre-slaughter
      –   Low-Pathogenic AI H5N1
      –   Culled 54,000 birds, 100% reimbursed


 •   Take home message - surveillance works




http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jul0907birds.html
 Public Opinion
    AP-Ipsos poll June 2007 vs 2006
     “bird/avian flu”
         27% concerned vs 35%
         41% not concerned vs 31%
         56% read/heard/seen coverage vs 74%
         62% govt giving enough attention vs 42%
         Could affect funding




http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jul0607ipsos.html
 H5N1 Pandemic Risk
 –   Influenza A transmission in SE Asia
      •   Less predictable seasonality
      •   Multiple peaks, high activity lasts longer
      •   Take home: Pandemic could be hatched any
          time of year
 •   2 critical mutations identified (in lab test)
      •   Enhance human transmission
      •   Will help with surveillance in virus isolates
      •   Know better what to look for

Lancet Infect Dis 2007;7(8):543-8
Yang. Science 2007;317:825
 Pandemic Stockpile as of 7/18/07
    Vaccine
         7.25M people (14.5M doses) H5N1 vaccine
              Approved product Sanofi Pasteur + GSK (2.3M)
              For “those who would be at the highest risk of exposure
               to the virus in the early critical months of a pandemic”
    Antiviral
         48M courses oseltamivir & zanamivir (state and
          fed)
    Personal Protective Equipment (PPE)
         104M N-95 respirators
         52M surgical masks

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jul1907update.html
 Antivirals Update
    Oseltamivir safety
         Studies initiated to evaluate neuro side effects
    New agent
         T705 - targets polymerase
         Phase II to start in late 2007




http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jun2007drugs.html
 Antiviral Resistance Issues
    H5N1 becoming less susceptible to
     oseltamivir
         Clade 1 (Cambodia) domestic birds, 6-7 fold less
          susceptible 2004-2005
         Clade 2 (Indonesia) 25-30 fold less susceptible
          than 2004 Clade 1
         Maintained virulence/fitness
         Resistance may be avoided using 2.5 fold higher
          dose
         WHO in process of revising antiviral
          recommendations


http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jun2207resist.html
 Pandemic Vaccine Update
    FDA approved first H5N1 vaccine
         Sanofi Pasteur
         In stockpile
    FDA approval process fast-tracked
    More H5N1 vaccines ordered for stockpile
         GSK – with adjuvant, much more potent
         Novartis
    New H5N1 vaccine trials
         DNA, cell-culture
    Universal influenza A vaccine progress
         No need annual re-vaccination
         Acambis-FLU-A Universal Vaccine
              Recombinant target M2 protein (M2e extracellular domain)
              Phase I announced 7/30/07
              Also assess adjuvants


http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jul3007acambis.html
 Universal Vaccine Update
    Vaccine production capacity
         Sanofi Pasteur building new plant
              By 2008-09 annual dose capacity 50M  150M
         Retrofit facilities for “warm base”
              Sanofi Pasteur and MedImmune
              2-5 year commitment “on call”
              Allow year-round pandemic vaccine production
         Anticipate 300M total U.S. capacity by 2012




http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jun2007vaccine.html
 Non-Pharmaceutical Interventions
    1918 pandemic NPIs used in 43 major cities
    3 main interventions
         Isolation & Quarantine
         School closings
         Bans on public gatherings
    Estimated excess pandemic deaths
    Results
         All cities used at least one of the main 3 NPIs
         Most used combination – school close & public gathering ban
         Took 10 days for NPI to affect mortality rates
         NPI use associated with fewer excess deaths
         Combinations (especially school close and public gatherings)
          best
         Rapid initiation generally better


Markel. JAMA 2007;298:
Community Mitigation
Extremely Drug Resistant
  (XDR) Tuberculosis
What is TB
   Bacterial infection
   Prevalence – 2 Billion (1/3 global population)
   Passed person-person by coughing
       Aerosol transmission
       Infection in the lung – asymptomatic (latent TB)
       10% re-activate to cause pneumonia
   Difficult to treat
       Requires 4 drugs for 6-12 months
       DOT
   Interaction with HIV/AIDS – partners in crime
 TB Prevalence




www.tbalert.org/worldwide/images/
 TB Disease




www.stanford.edu
Medications to Treat TB
   1st line drugs
       Isoniazid (INH)
       Rifampin
       Pyrazinamide
       Ethambutol
   2nd line drugs
       5 options
 Multidrug Resistant (MDR) TB
    1st line drugs
         Isoniazid (INH)
         Rifampin
         Pyrazinamide
         Ethambutol
    2nd line drugs
         5 options


    Prevalence – estimated 500,000 in 2004

http://www.who.int/tb/xdr/faqs/en/index.html /
 Extremely Drug Resistant (XDR)
    MDR TB plus resistant to two 2nd line drugs
        Disease same as regular TB but…
        Essentially untreatable with medications alone
        Surgery often required
        Case fatality >70%
    Unknown prevalence
        Rough global estimate 25-30,000
        49 known cases in U.S. 1993-2006



CDC. MMWR 2007;56:250
XDR vs. Pandemic Flu
   Similarities
       Person-person transmission
       High mortality
       Potential for large numbers infected/affected
   Differences
       Low attack rate
       Long latency period
       Slow spread
       N-95 (or better) respirator for protecting
        healthcare workers
Resources
 International – WHO                    (www.who.int/en)

 Federal – DHHS, CDC                       (www.cdc.gov)
                                    (www.pandemicflu.gov)
 State – MODHSS                       (www.dhss.mo.gov)

 Regional
       Local Health Depts     (www.co.st-louis.mo.us/doh)
                       (stlouis.missouri.org/citygov/health)
       SLU Vaccine Ctr       (medschool.slu.edu/vaccine)
       Washington University SOM (medicine.wustl.edu)
       MRCE                             (mrce.wustl.edu)
       SLU Institute Bio-Security  (bioterrorism.slu.edu)

								
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