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

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

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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

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    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
    • 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
      • 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