Training Kit for

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Training Kit for Pandemic Influenza
Unit 8 - Vaccines Anti-virals
Prepared by Infectious Disease Control Training
Centre, Hospital Authority Infection Control
Branch, Centre for Health Protection, Department
of Health

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By the end of this unit, you will be familiar
with
Objective

• the current influenza vaccine
• the pandemic influenza vaccine, and its
  difference from the current influenza vaccine
• the use of anti-viral medication Oseltamivir
  (Tamiflu) Zanamivir (Relenza) in pre-exposure
  prophylaxis, treatment, post-exposure
  prophylaxis

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Rationale
Current Influenza Vaccine

• Most people are ill with flu for a few days
• Some may get more severe symptoms or be even
  fatal
• Especially elderly, chronic illnesses
  immunocompromized
• Flu vaccine is documented to reduce infection and
  complication rates

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WHO recommendation for influenza vaccine for the
year 2008/2009
Current Influenza Vaccine

• Northern hemisphere
• A/Brisbane/59/2007 (H1N1)-like virus
• A/Brisbane/10/2007 (H3N2)-like virus
• B/Florida/4/2006-like virus

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Timing of flu vaccine
Current Influenza Vaccine

• Vaccine composition is updated every year
• Protection develops about 2 weeks after
  vaccination
• The best time for vaccination is October to
  December for northern hemisphere

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Current Influenza Vaccine

• Current influenza vaccine against circulating
  H3N2 and H1N1 strains is not effective against
  H5N1 and other types of Avian influenza virus
• By providing the seasonal human influenza vaccine
  to people at risk for avian influenza, the risk
  of co-infection with avian and human influenza
  virus and the possibility of genetic
  re-assortment could be decreased

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Pandemic Strain Vaccine

• Vaccine against influenza pandemic
• Production starts after the pandemic virus has
  been recognized

• Vaccine supplies may not be available at the
  early months of a pandemic (Vaccine development
  takes 4 6 months)

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Goals of Antiviral Agents in Different Phases of
Pandemic
Use of Anti-virals

• Interpandemic Period
• To reduce risk of human infection from exposure
  to animal virus
• Pandemic Alert Period
• To contain or delay spread, to avert a pandemic
  and gain time to implement pandemic response
  measures
• Aggressive use of antivirals
• Pandemic Period
• To reduce morbidity and mortality and to preserve
  healthcare system effectiveness
• Selective use of antivirals

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Considerations in Antivirals Use
Use of Anti-viralsSeasonal Flu

• For seasonal influenza
• Oseltamivir (Tamiflu) and Zanamivir (Relenza) are
  active for treatment and prophylaxis of influenza
  
• (Both are licensed in HK for treatment and
  prophylaxis against influenza)
• Systemic bioavailability
• Oseltamivir at least 75 Zanamivir 10-20
• Reduction in length of illness
• Start of therapy within 0 12 hours 3.1 4.1
  days
• Start of therapy within 12 36 hours 1 - 2 days
• Start of therapy within 36 - 48 hours 0.5 days

SEASONAL FLU
Source Moscona A. Neuraminidase inhibitors for
influenza. NEJM 2005 353 1363-73
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SEASONAL FLU
Use of Anti-viralsSeasonal Flu

• Clinical indications for the use of oseltamivir
  for seasonal influenza
• For out-patients
• Presented within 48 hours of onset of fever AND
• With laboratory evidence of influenza infection
  e.g. positive influenza rapid antigen test AND
• At high risk of developing severe complications
• 65 years or children between 1-2 years old
• Chronic cardiovascular diseases excluding
  hypertension
• Chronic respiratory illness including asthma and
  COAD
• Chronic liver/renal diseases
• Diabetic patients with complications
  (nephropathy neuropathy and/or retinopathy)
• Immunocompromised patients
• Children gt2 to 12 years old taking long term
  aspirin
• Note Pregnant women should only be given
  oseltamivir if the potential benefit justifies
  the potential risk to the fetus, e.g. those with
  concurrent medical diseases as listed above

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SEASONAL FLU
Use of Anti-viralsSeasonal Flu

• Clinical indications for the use of oseltamivir
  for seasonal influenza
• For in-patients
• Presented within 48 hours of onset of fever AND
• With laboratory evidence of influenza infection
  e.g. positive influenza rapid antigen test AND
• Admitted because of
• Complications of influenza
• e.g. pneumonia, myocarditis, pericarditis,
  myositis, encephalitis, Guillain-Barre syndrome
  and Reyes syndrome (associated with aspirin
  therapy) or
• Other conditions and who also belong to the high
  risk group listed above

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H5N1
Use of Anti-viralsH5N1

• For H5N1 virus
• Recent H5N1 isolates have been reported to be
  resistant to M2 inhibitors (e.g. amantadine)
• H5N1 virus are susceptible in vitro to
  oseltamivir and zanamivir
• Oral oseltamivir and topical zanamivir are active
  in animal models of H5N1 virus infection
• Optimal dose and duration of treatment with
  neuraminidase inhibitors are uncertain

• The following treatment and prophylaxis regimens
  during pandemic influenza are the recommendations
  of the Scientific Committee of Emerging and
  Zoonotic Diseases (SCEZD) of the Centre for
  Health Protection (CHP) which are based on the
  experience in infections with usual human
  influenza strains

Source The Writing Committee of the WHO
Consultation of Human Influenza A/H5. Avian
influenza (H5N1) infection in humans. NEJM
20053531374-85 Source CHP General Guide To
Doctors Antiviral Use For Novel influenza
Treatment Prophylaxis http//www.chp.gov.hk/file
s/pdf/grp_hp_guidelines_af_draft_general_20guide_
to_doctors.pdf
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Treatment Aim ? Morbidity Mortality
Use of Anti-viralsH5N1

• To be given as soon as possible, preferably
  within 48 hours after the onset of symptoms for
  maximum efficacy

• Antiviral treatment with oseltamivir, if given
  late, may be ineffective (NEJM 20043501179-88)
• Oseltamivir (Tamiflu)
• Adult ?13 yr old 75mg BD x 5 days
• 1-12 yr old 2mg/kg BD x 5 days
• For ease of administration as recommended by the
  manufacturer
• 15 kg 30mg BD x 5 days
• gt15 - 23 kg 45mg BD x 5 days
• gt23 - 40kg 60mg BD x 5 days
• gt40 kg 75mg BD x 5 days
• Trial of high dose oseltamivir (e.g. 150mg BD for
  adults) to be considered on a case by base basis
  and preferably under clinical trial setting

• Zanamivir (Relenza)
• Adult gt7 yr old 10mg BD x 5 days

H5N1

• The information in this slide is the
  recommendation of the SCEZD of the CHP which is
  based on the experience in infections with usual
  human influenza strains

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Stratified exposure risk
Use of Anti-viralsH5N1

• Moderate risk exposure involved in e.g.
  intubation, nebulization, tracheal suction
  (oseltamivir might be administered)
• High risk exposure Household or close family
  contact (oseltamivir should be administered)
• Low risk exposure healthcare workers not in
  close contact (unprotected distance gt 1 metre /
  having no direct contact), oseltamivir should
  probably not be administered.

H5N1

• The information in this slide is the
  recommendation of the SCEZD of the CHP which is
  based on the experience in infections with usual
  human influenza strains

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Pre-exposure prophylaxis May Offers Protection
Use of Anti-viralsH5N1

• Target groups
• Health Care Workers with at least moderate risk
  of exposure (Emergency response level)
• Essential service providers (Emergency response
  level)
• Cullers (Serious Response level or above)
• Recommended Dosage
• Oseltamivir 75mg daily po for 7-10 days after the
  last exposure (WHO weak recommendation)
• The safety and efficacy of prophylactic use of
  oseltamivir have been demonstrated for continued
  use for up to 8 weeks
• The protection will cease when the individual
  stops taking the prophylaxis

H5N1

• The information in this slide is the
  recommendation of the SCEZD of the CHP which is
  based on the experience in infections with usual
  human influenza strains

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Post-exposure prophylaxis Aim at Outbreak
Control
Use of Anti-viralsH5N1

• Useful during the early phase of the pandemic for
  outbreak control and to minimize further
  spreading of the disease
• Target groups (health care workers or community
  contacts)
• High risk exposure (WHO strong recommendation)
• Moderate risk exposure (WHO weak recommendation)
• Recommended dosage and duration (Oseltamivir)
• As soon as possible with the last contact falls lt
  7 days
• gt 13 years old 75mg daily po
• lt 13 years old 15 kg 30mg daily po
• gt15 - 23 kg 45mg daily po
• gt23 - 40kg 60mg daily po gt40 kg 75mg daily
  po
• WHO recommended that oseltamivir should be
  continued for 7-10 days after the last known
  exposure
• May extend to 14 days if continuous spread in the
  source environment (e.g. in closed institutions)

H5N1

• The information in this slide is the
  recommendation of the SCEZD of the CHP which is
  based on the experience in infections with usual
  human influenza strains

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Post-exposure prophylaxis - alternatives

• Zanamivir might be considered as an alternative
  for health care worker without preexisting airway
  disease
• 2 inhalations 5 mg daily for 7 10 days after
  the last known exposure (WHO weak recommendation)
• Safety and efficacy have been demonstrated for up
  to 4 weeks of continued use.

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Post-exposure prophylaxis - alternatives

• M2 blockers (Amantadine/Rimantadine) may have a
  potential role for prophylaxis if neuraminidase
  inhibitors are not available and the pandemic
  strain is sensitive. (WHO weak recommendation)
• Age Amantadine dose
• 1-9 years 5mg/kg/day up to 150 mg in 2 divided
  dose
• 10-64 years 100 mg BD
• gt65 years lt100 mg daily
• It should be continued for 7 10 days after the
  last known exposure
• Safety and efficacy have been demonstrated for up
  to 6 weeks of continued use.
• Avoided in patients with seizure disorders or
  receiving neuropsychiatric treatment.

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Drug Information - Tamiflu
Use of Anti-virals

• Special Precautions
• taken with meals to reduce gastrointestinal side
  effects
• Severe renal impairment
• 1. ClCr 10-30mL/min dose adjustment required.
• 2. CrCl lt10mL/min has not been studied
• Pregnancy FDA Risk C (Risk cannot be ruled
  out)
• WHO risk of birth defects/ spontaneous
  abortion
• Lactation unknown/not recommended
• Fructose intolerance (Powder for oral suspension)

Source MIMS on line Source WHO Guidelines on
the Use of Vaccines and Antivirals during
Influenza Pandemics Source UpToDate online
version 16.3
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Drug Information - Relenza
Use of Anti-virals

• Contraindication
• Hypersensitivity
• Special Precautions
• Pregnancy FDA Risk C (Risk cannot be ruled
  out)
• Lactation Excretion in breast milk
  unknown/use caution
• Underlying airways disease e.g. asthma, COPD
• Due to possibility of bronchospasm (rare lt1.5)

Source MIMS on line Source UpToDate online
version 16.3
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Adverse Effects
Use of Anti-virals
ReferenceMoscona A. Neuraminidase Inhibitors for
Influenza. N Engl J Med 2005 3531363-73
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Conclusion
Sporadic cases No human-to-human transmission
Clusters of cases Inefficient human-to-human
transmission
On-going cluster related transmission Substantial
pandemic risk
Pandemic
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End of Unit 8