Seasonal influenza - current perspective with special reference to India - aug 2011
Upcoming SlideShare
Loading in...5
×
 

Seasonal influenza - current perspective with special reference to India - aug 2011

on

  • 1,969 views

This presentation is more for the general doctors, including Ob/gyn, medical specialists etc. and was formulated as a presentation for Chandigarh Nursing Home Association meeting in Aug 2011 using ...

This presentation is more for the general doctors, including Ob/gyn, medical specialists etc. and was formulated as a presentation for Chandigarh Nursing Home Association meeting in Aug 2011 using material provided by Chiron/ Novartis

Statistics

Views

Total Views
1,969
Views on SlideShare
1,969
Embed Views
0

Actions

Likes
1
Downloads
43
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Seasonal influenza - current perspective with special reference to India - aug 2011 Seasonal influenza - current perspective with special reference to India - aug 2011 Presentation Transcript

  • Influenza Disease & Vaccination: Current Perspective with special reference to India
    Dr. Gaurav Gupta, Practising Pediatrician
    Member AAP, IAP
    Charak Clinics, Mohali, Punjab
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
    View slide
  • H1
    H1N1
    A
    16 HA proteins
    H2
    H1N2
    Orthomyxoviridae family
    B
    H2N1
    N1
    9 NA proteins
    C
    H2N2
    N2
    Influenza virus has several subtypes!
    Influenza is a member of the Orthomyxoviridae family of viruses
    • Influenza A and B cause seasonal epidemics, C mainly causes mild respiratory illness View slide
    • Influenza A is divided into subtypes based on the HA and NA proteins
    • HA and NA genes can be reassorted (switched) between strains generating novel subtypes
    Different influenza A subtypes result from differentcombinations of the HA and NA proteins
    HA, hemagglutinin; NA, neuraminidase
  • Influenza infection has a variety of symptoms!
    Clinical symptoms
    Influenza infections are asymptomatic in30–50% of cases
    Common symptoms include abrupt onset of fever (38–40°C), sore throat, unproductive cough, runny or stuffy nose, headache, myalgia, chills, anorexia and extreme fatigue
    Uncommon symptoms include photophobia, abdominal pain and diarrhea
    Illness improves in under 7 days, cough and malaise may persist for weeks
    Children may experience high fevers that can lead to febrile seizures
    Fever may be absent in the elderly; presenting signs may include anorexia, lassitude or confusion
    Virus shedding
    Adults: from the day before symptoms appear until 5 days after illness onset
    Young children: several days before illness onset until >10 days afterwards
    Severely immunocompromised patients: weeks to months
    Influenza virus particles (brown) invade cilia (blue) in the airways
    Symptoms associated with seasonal influenza are well defined and can vary between individuals
    Zambon MC. J Antimicrob Chemother 1999; 44 (Suppl. B):3-9; CDC, Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep 2007; 56:1-54.
  • Clinical Differentiation Between the Common Cold and the Flu
    The following symptoms are more commonly seen in influenza rather than the common cold:
    High fever lasting 3 to 4 days
    Headache
    Myalgia
    Fatigue and weakness
    Extreme exhaustion
    Severe chest discomfort and cough
    The following symptoms are more commonly seen in the common cold rather than influenza:
    Stuffy nose is common
    Sneezing is common
    Cough is generally mild to moderate
    Symptoms such as fever, headache, aches and pains and exhaustion are rare in those with colds.
  • Influenza viruses are spread by virus-laden aerosols!
    How influenza viruses are spread:
    From person to person primarily through large-particle respiratory droplet transmission
    Requires close contact betweensource and recipient as droplets only travel <1m
    By contact with surfaces contaminated with respiratory droplets
    By airborne transmission of evaporated droplets that may remain in the air for long periods of time (data are limited)
    Virus transmission may be slowed by social distancing
    CDC, Epidemiology and prevention of vaccine-preventable diseases. Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. 10th ed. Washington DC: Public Health Foundation; 2007:235-56; Rust MJ, et al.Nat Struct Mol Biol 2004; 11:567-573; CDC, Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep 2007; 56:1-54.
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Influenza virus changes due to antigenic drift or shift!
    Antigenic drift
    Antigenic shift
    NA
    HA
    NA
    HA
    A/H1N2
    Geneticmutations
    A/H1N1
    A/H1N1
    Geneticressortment
    A/H3N2
    A/H3N1
    Antigenic drift occurs when there are small changes in the virus
    Antigenic drift produces new virus clades that may not be recognized by the immune system, meaning reinfection can occur
    Drifted strains may be mismatched with seasonal influenza vaccine
    Antigenic shift is a major change in the influenza A virus, altering the HA and/or NA proteins
    Antigenic shift leads to the emergence of a new influenza A subtype
    Most people have little or no protection against the new virus
    Antigenic drift can lead to epidemics; antigenic shift can lead to pandemic influenza
    Cox NJ, Subbarao K. Annu Rev Med 2000; 51:407-421; Zambon MC. J Antimicrob Chemother 1999; 44 (Suppl. B):3-9; Koelle K, et al. Science 2006; 314:1898-1903.
  • 1918Spanish
    1957
    Asian
    1968
    Hong Kong
    1977
    Russian
    1999
    Hong Kong
    1997
    Hong Kong
    2003-2008
    Global
    2003
    Dutch
    2009
    Global
    H1N1
    H2N2
    H3N2
    H1N1
    H9N2
    H5N1
    H7N7
    H5N1
    H1N1
    2 cases
    18 cases
    82 cases
    387 cases
    ~30,000 cases
    >50 million deaths
    ~2 million deaths
    ~1 million deaths
    <1 million deaths
    Six deaths
    One death
    245 deaths
    145 deaths
    1918
    1957
    1977
    2000
    2008
    1968
    2009
    Pandemic outbreaks
    Pandemic
    Recent outbreaks of influenza
    Influenza pandemics & emerging new pandemic threats exist since 1900!
    • The circulation of H5N1 in poultry and its high fatality rate have raised concerns over an H5N1 pandemic if this virus acquires the capacity for sustained human-to-human transmission
    • Transmission dynamics are described using the reproductive number (R0) and case fatality ratio, which may vary depending on country and season
    The emergence of H1N1 has demonstrated the difficulty in predicting pandemics
    Nicholson KG, Wood JM, Zambon M. Lancet 2003; 362:1733-1745; WHO, Cumulative number of confirmed human cases of avian influenza A/(H5N1), available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_09_10/en/index.html(accessed 5 November 2008); CDC, Avian Influenza, available at: http://www.cdc.gov/flu/avian/outbreak.htm (accessed 5 November 2008).
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Swine
    New Reassorted
    virus
    Emergence of Swine Flu Virus
    Avian
    virus
    Avian
    Reservoir
    Human
    virus
    Other
    mammals?
  • Pandemic H1N1 rapidly spread worldwide: April 2009
    April 2009
    START
    March 2009
    Cumulative cases
    1-10
    11-50
    51-500
    >500
    • The H1N1 pandemic was first reported by the US and Mexico on 26 April 2009
    • Phase 4 of pandemic alert was declared on 27 April, and Phase 5 on 29 April
    • By 30 April, 257 cases including eight deaths had been reported in 11 countries
    WHO, H1N1 number of laboratory confirmed cases, available at http://gamapserver.who.int/h1n1/atlas.html (accessed 30 April 2009); WHO, H1N1 cases, situation update 6, available at http://www.who.int/csr/don/2009_04_30_a/en/index.html (accessed July 2009).
  • Pandemic H1N1 rapidly spread worldwide: May 2009
    April 2009
    May 2009
    START
    March 2009
    Cumulative cases
    1-10
    11-50
    51–500
    500-5,000
    >5,000
    29 May *, 15,510 cases including 99 deaths reported by 53 countries
    * Date of last report for May 2009. WHO, H1N1 number of laboratory confirmed cases, available at: http://gamapserver.who.int/h1n1/atlas.html (accessed 29 May 2009); WHO, H1N1 cases situation update 41, available at http://www.who.int/csr/don/2009_05_29/en/index.html (accessed July 2009).
  • Pandemic Influenza : Status in 2010
    http://www.who.int/csr/don/2010_07_09/en/index.html
  • Influenza virological Surveillance (ILI) from 1st week Dec 2010 till now
    http://gamapserver.who.int/GlobalAtlas/sharedFunction/sharedFunctionInterface.asp?displayType=map
  • Influenza : % positive cases & virus subtypes
    http://www.who.int/csr/don/2010_07_09/en/index.html
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of current pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Seasonal Influenza : elevated risk for complications is associated with both age extremes!
    Infection rates for seasonal influenza are highest among children1
    Elderly are at high risk of complications from seasonal influenza
    • Exacerbation of underlying chronic pulmonary and cardiovascular diseases3
    • Complication rate higher for subjects with chronicheart disease (46.9%) vs. those without (22.8%)4
    In hospitalized children:
    Febrile seizures reported by 6-20%1
    Intensive care required by 4-11%1
    80% were <5 years of age; 27% were <6 months of age1
    Cumulative hospitalization rates for laboratory-confirmed influenza among children 0-4 and 5-17 years of age, by season, US2
    Annual rates of influenza-associated cardiorespiratory hospitalizations in those ≥50 years of age, US5
    Age range (years)
    Season
    1,000
    5
    2004-05 0-4
    2005-06 0-4
    2006-07 0-4
    2007-08 0-4
    800
    4
    600
    3
    Hospitalization rate per 10,000 person-years
    2004-05 5-17
    2005-06 5-17
    2006-07 5-17
    2007-08 5-17
    Population-based rate
    2
    400
    1
    200
    0
    0
    50-64
    65-69
    70-74
    75-79
    80-84
    40
    42
    44
    46
    48
    50
    52
    2
    4
    6
    8
    10
    12
    14
    16
    18
    Age (years)
    Week
    1. CDC, 2010 Yellow Book, available at http://wwwn.cdc.gov/travel/yellowbook/2010/chapter-2/influenza-seasonal-avian-pandemic.aspx (accessed August 2009). 2. CDC, Mortality and Morbidity Weekly Report 2009; 58:369-374. 3. Bridges CB, et al. Inactivated influenza vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th ed. Philadelphia: Saunders; 2008. 4. Irwin DE, et al. BMC Health Serv Res 2001; 1:8. 4. Thompson WW, et al. JAMA 2004; 292:1333-1340.
  • The majority of pandemic H1N1 cases have occurred in subjects <20 years of age!
    Seasonal influenza attack rates and proportionof population at high risk of serious complications, by age (US)1
    Age distribution and travel status of pandemic H1N1 2009 cases in EU and EEA countries2
    Higher incidence of pandemic H1N1 than seasonal influenza
    in age group 10-19 years
    2,500
    60
    Gross attack rate
    At high risk ofserious complications
    50
    2,000
    Travel related
    Domestic
    The high level of domestic cases indicates community-level spread of the virus, meeting the WHO criteria for Phase 6 pandemic alert3
    40
    1,500
    Proportion of population (%)
    Number of cases
    30
    1,000
    20
    500
    10
    0
    0
    0-4
    5-17
    18-49
    50-64
    65+
    ≥60
    50-59
    40-49
    30-39
    20-29
    10-19
    0-9
    Age group
    Age group
    N=7,681 cases reported by 28 EU/EEA countries as of 6 July 2009
    H1N1 pandemic influenza is predominantly found in patients <20 years of age; in contrast, the very young and the elderly are most at risk from seasonal influenza
    1. Molinari NA, et al. Vaccine 2007; 25:5086-5096. 2. ECDC Surveillance Report, Analysis of Influenza A(H1N1)v individual case reports in EU and EEA countries, Update 9 July 2009. 3. WHO, Current WHO phase of pandemic alert, available at http://www.who.int/csr/disease/avian_influenza/phase/en/ (accessed July 2009).
  • Age sex pattern of H1N1 cases in India
    http://mohfw-h1n1.nic.in/documents/PDF/EpidemiologicalTrendsInIndia.pdf
  • Win – Win Situation vaccinating Pregnant Women
    ACIP/ CDC/ ACOG recommend Flu vaccination during pregnancy
    Can be done at any gestational age, earlier the better.
    Benefits mothers by reducing serious respiratory infections during pregnancy
    Benefits fetus – Better weight gain & decreased incidence of SGA
    Benefits infant – the most effective way to prevent influenza in the first 6 months of life.
  • Influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of current pandemic H1N1
    Defining at-risk populations
    Influenza Vaccine – Data from Chandigarh
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Methodology-Clinical Effectiveness Study
    25
  • Continued…..
    Methodology-Clinical Effectiveness Study
    26
  • Continued…..
    Methodology-Clinical Effectiveness Study
    27
  • Overall Results
  • Clinical Effectiveness of Influenza vaccine-1
    Fully vaccinated cohort (n=154) vs. Unvaccinated cohort (n=330)*
    Conclusion: Influenza vaccine is effective in reducing the ILI and visits to physician for ARI in fully vaccinated Indian children as compared to unvaccinated children.
    *Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
  • Clinical Effectiveness of Influenza vaccine-2
    Partially vaccinated cohort (n=16) vs. Unvaccinated cohort (n=330)*
    Conclusion: Partially vaccinated children had no significant protection against ILI and visits to physician as compared to unvaccinated children.
    *Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
  • Clinical Effectiveness of Influenza vaccine-3
    Age-wise efficacy for prevent of ILI*
    Conclusion: Children aged 3-9 year had the best protection rates against ILI as compared to unvaccinated children.
    *Renuka R, Gupta G, Tiwari P. Clinical effectiveness of the 2010-2011 seasonal influenza vaccine among healthy Indian children. WSPID-2011, Melbourne.
  • Comparative Vaccine Effectiveness
    * Singh H, Gupta G, Tiwari P. Clinical effectiveness of the 2009-2010 seasonal influenza vaccine among healthy Indian children. ISPOR 4th Asia Pacific Conference, Phuket, Thailand.
  • Safety and Tolerability of Influenza vaccine-1
    Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
  • Safety and Tolerability of Influenza vaccine-2
    *Singh H, Gupta G, Tiwari P. Safety and tolerability of trivalent inactivated influenza (TIV) vaccine in healthy Indian children. 62nd Indian Pharmaceutical Congress, 2010. Manipal, India. (Poster No. L-6).
  • Pandemic influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of current pandemic H1N1
    Defining at-risk populations
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • Influenza Vaccines are representative of virus strains circulating in India as well
    WHO Influenza Global Surveillance Network
    • The network was established in 1952
    • Currently, WHO have 128 institutions from 99 countries as recognized National Influenza centers
    Objectives:
    Surveillance enables to recommend twice the content of Influenza vaccine for the season
    Serves as a global alert mechanism for the emergence of Influenza virus with Pandemic potential
    1 Laboratory
    New Delhi
    AIIMS
    ≥ 2 Laboratory
    Dibrugarh
    V P Chest
    RMRC
    No Laboratory
    Nagpur
    IGGMC
    Kolkata
    Mumbai
    NICED
    Haffkine Inst
    Pune
    NIV
    RegionalCenters
    Vellore
    Chennai
    CMC
    NewCenters
    KIPM
    ReferralCenter
  • Pandemic Flu protection added to Seasonal flu vaccine
    WHO Influenza strain for Northern Hemisphere 2010 – 2011 season:
    an A/California/7/09 (H1N1)-like virus; *
    an A/Perth /16/2009 (H3N2)-like virus; **
    a B/Brisbane/60/2008-like virus.*** 
    *A/California/7/09 (H1N1)-like virus is the pandemic (H1N1) 2009 influenza virus.  A monovalent vaccine containing this strain was made available to the United States in the fall of 2009.
    **A/Perth/16/2009 (H3N2)-like virus is a change from the 2009-2010 influenza vaccine formulation.
    ***and B/Brisbane /60/2008-like virus is a current vaccine virus.
    http://www.who.int/csr/disease/influenza/recommendations201010north/en/
  • ACIP Recommendations for seasonal Influenza vaccination 2010-11
    1. A recommendation that annual vaccination be be administered to every individual aged ≥6 months for the 2010-11 influenza season
    2. Children and adolescents at higher risk for influenza complications
    • ! Are aged 6 months–4 years (59 months);
    • ! Have chronic pulmonary, cardiovascular, renal, hepatic, cognitive, neurologic/neuromuscular,
    • hematological or metabolic disorders (including diabetes mellitus)
    • ! Are immunosuppressed (Caused by medications or by HIV)
    • ! Are receiving long-term aspirin therapy and therefore might be at risk for experiencing Reye syndrome after influenza vaccination
    • ! Are residents of long-term care facilities; and
    • ! Will be pregnant during the influenza season.
    Source: CDC recommendation available at http://www.cdc.gov/flu
  • Pandemic influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of current pandemic H1N1
    Defining at-risk populations
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • WHO Recommended strains 2011 -12 season
    It is recommended that vaccines for use in the 2011-2012 influenza season (northern hemisphere) contain the following:
    an A/California/7/2009 (H1N1)-like virus;
    an A/Perth/16/2009 (H3N2)-like virus;
    a B/Brisbane/60/2008-like virus.
    A/H3N2
    B
    A/H1N1
    California
    Brisbane
    Perth
    Brisbane
    Brisbane
    Brisbane
    2009-10
    2011- 12
    2010-11
    2011-12 season WHO recommended strain are similar to 2010-11 season northern hemisphere strains
  • WHO monitors strain drifts and recommends strains for vaccine inclusion
    Drift has led to 15 changes in recommended strains since 1997-19981,2
    A/H3N2
    B
    A/H1N1
    Bayern
    Beijing
    NewCaledonia
    Brisbane
    SolomonIslands
    Brisbane
    Wuhan
    Sydney
    Moscow
    Fujian
    Wisconsin
    California
    Sichuan
    Beijing
    Malaysia
    Hong Kong
    Florida
    Shanghai
    1997-98
    2007-08
    2005-06
    2001-02
    2002-03
    2003-04
    2006-07
    1998-99
    2004-05
    1999-00
    2000-01
    2008-09
    Influenza Season (year)
    For the Northern hemisphere, the recommended strains have changed 12 times since 1997-1998
    1. www.who.int; 2. http://www.fda.gov/cber/flu/flu2008.htm.
  • Key Questions
    Question 1
    Is annual vaccination reqd. if the strain remains the same for consecutive years?
  • Yes, we require annual Influenza Vaccination if vaccine strains remain the same which is well supported by:
    • Local guidance
    • International guidance
    • Guidance from a standard textbook
  • Key Questions
    Question 2
    What is the best time to give the Influenza vaccine in India?
  • Northern hemisphere
    Tropics
    Southern hemisphere
    45
    1
    29
    41
    25
    37
    5
    9
    13
    17
    21
    33
    49
    Week
    Influenza spread occurs inseasonal patterns
    10
    Influenza activity peak: November-March2,3
    8
    6
    ILI/1000 Population
    4
    2
    0
    E.g. India
    1
    3
    5
    7
    9
    11
    13
    15
    40
    42
    44
    46
    48
    50
    52
    Week
    50
    40
    30
    ILI/1000 Population
    Year-round activity3,4
    20
    10
    0
    J F M A M J J A S O N D
    Month
    20
    18
    16
    14
    ILI Consultations/1000 Population
    12
    Influenza activity peak: April-September4,5
    10
    8
    6
    Globe image: www.phimap.com
    4
    2
    0
    ILI = influenza-like illness.
    1. Bridges et al. 2008; 2. EISS 2004; 2. Cox and Subbarao 2000; 4. CHP 2008; 5. Yohannes et al. 2003.
  • Pandemic influenza: An overview!
    General introduction to influenza viruses and infection
    Influenza outbreaks and pandemics
    Analysis of current pandemic H1N1
    Defining at-risk populations
    Influenza Vaccines Recommendations 2010-11 season
    Influenza Vaccines Recommendations 2011-12 season
    Influenza Vaccines
  • How Influenza vaccines are made
    WHO Influenza Global Surveillance Network
    • The network was established in 1952
    • Currently, WHO have 128 institutions from 99 countries as recognized National Influenza centers
    Objectives:
    Surveillance enables to recommend twice the content of Influenza vaccine for the season
    Serves as a global alert mechanism for the emergence of Influenza virus with Pandemic potential
    1 Laboratory
    ≥ 2 Laboratory
    No Laboratory
    Seasonal influenza vaccines are trivalent vaccines derived from the three viral types that are currently in global circulation
    http://www.who.int/csr/disease/influenza/surveillance/en/index.html
  • Types of Influenza Vaccines
    • Live Attenuated Influenza Vaccine
    • Inactivated Influenza Vaccine
    • Whole virus vaccines
    • Split-virion Vaccine
    • Subunit vaccine
    • Adjuvanted vaccines
    • Virosomal vaccines
    • Cell culture derived vaccines
    A) whole-virus, B) split-virion, C) subunit, D) virosomal, E) adjuvanted.
    Amorij JP, Huckriede A, Wilschut J, Frijlink HW, Hinrichs WL. Development of stable influenza vaccine powder formulations:
    Challenges and possibilities. Pharm Res. 2008;25(6):1256-1273.
  • Comparison of Influenza Vaccines
    +Low; ++ Medium; +++ High.
  • Live vs Inactivated Influenza Vaccine
    http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5213a1.htm
  • Thank You