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Influenza Virus
Acute respiratory illness caused by infection with influenza viruses Family Orthomyxoviridae Types - Influenza A, B & C viruses Influenza A & B viruses - most commonly cause human disease
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Influenza A Virus
NA HA
PB1 M1 M2
PA
PB2
RNA NP
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Cox R.J et al., Scandinavian Journal of Immunology 2003; 59: 115
Neuraminidase (N or NA)
Degrades the receptor Allows release of newly formed viruses from infected cell Immune responses to N antigen limit viral spread & contribute to reduction of infection
M1 protein
Matrix protein which forms the viral capsid Stabilization of lipid envelope and in virus assembly
M2 protein channel
Functioning as an ionchannel (energy regulators)
Ribonucleoprotein
RNA (genetic code) Nucleoprotein (NP)
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Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
Epidemiology
Clinical Features
Antigenic Drift
Severe disease Mild disease generally confined to without older adults or seasonality person at high risk
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Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.
Mainly Airborne Aerosols (Coughs & Sneezes). Through direct contact : Animate or Inanimate. Incubation Period 18 72 h
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Epidemiology
Influenza outbreaks recorded virtually every year Global pandemics have occurred at variable intervals Most extensive & severe outbreaks caused by influenza A viruses Pandemics provide most dramatic evidence of impact of influenza A
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Influenza : Burden
As per World Health Organization : 3-5 million cases of severe influenza illness annually in industrialized countries, resulting in:
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http://mohfw-h1n1.nic.in
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Influenza Pandemics
1918 1957 1968 1977 2009
Spanish Severe Asian Severe Pandemic Pandemic H1N1 H2N2 50 million dead 2 million dead
Mild Pandemic
Since 1977, viruses of H1N1, H3N2 have circulated outbreaks of varying severity
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Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
Influenza A Epidemics
Begin abruptly, peak over 2- to 3-week period. Generally last for 23 months & subside rapidly. Temperate zones - during winter months . Tropics - throughout the year. Children with febrile respiratory illnesses, Influenza-like illnesses among adults. Hospital admissions - pneumonia, worsening of CHF & exacerbations of chronic pulmonary disease.
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Influenza B Outbreaks
Less extensive Less severe disease Less variation in subtypes Most frequently seen in schools and military camps
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Influenza
Clinical Manifestations
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Clinical Manifestations
Abrupt onset of systemic symptoms: Complications most frequently in:
Headache, feverishness, chills, myalgia, or malaise, cough & sore throat. Elderly>64 years. Chronic underlying medical disorders. Pregnancy , more so in 2nd or 3rd trimester. Children <2 years old
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine, 17th edition,. New York: McGraw-Hill Medical Publishing Division, 2008:749.
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Influenza : Prevention
Three time tested methods:
Avoid the Source. Remove the source. Strengthen your defences.
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Cover nose & mouth during cough or sneeze. Wash hands often with soap and water. If soap and water not available, use alcohol-based hand rub. Avoid touching eyes, nose & mouth. Try to avoid close contact with sick people. If sick with flulike illness :
Stay home for at least 24 hours after fever is gone except to get medical care or for other necessities.
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Prevention of Influenza
Most effective strategy for preventing influenza and its complications is : Annual Vaccination
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Prevention of Influenza
Vaccines
No No No
Yes
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CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
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Current vaccine trivalent preparation Influenza A (H1N1), Influenza A (H3N2), Influenza B viruses Protection is achieved Blymphocytes (antiHA and anti-NA antibodies). Specific immunity persists from 6 to 12 months
Vaccination
Serum antibodies peak between 2 & 4 months after vaccination but fall quickly
Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.
Influenza Vaccine
Clinical Efficacy
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43% reduction in absenteeism from work. 25% reduction in frequency of upper respiratory tract illness. Considerable cost savings. Reduction in mortality in those with chronic illnesses.
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Szucs T, J Antimicrobial Chemotherapy, 1999, 44: 11-15
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Nichol KL. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003; 21:17691775.
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Nichol KL. The efficacy, effectiveness and cost-effectiveness of inactivated influenza virus vaccines. Vaccine 2003; 21:17691775.
Effectiveness
Vaccine is Immunogenic in Healthy Adults & Elderly. Seroprotection rates for all 3 virus strains:
Healthy adults - 80 90% Elderly - > 70%
Mean fold increase [geometric mean of the intra-individual fold increases in HI titre (GMT)] for all 3 virus strains
Healthy adults > 10 Elderly > 6
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Zuccotti et al., Influvac, a trivalent inactivated subunit vaccine. Expert Opin. Biol. Ther 2011; 11 (1): 89:98
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Guidelines recommendation:
Coronary or other atherosclerotic vascular disease should be immunized with inactivated influenza vaccine
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Grau AJ, Urbanek C, Palm F Nat Rev Neurol. 2010 Dec;6(12):681-94. Epub 2010 Nov 9.
Case-control study involving 1,454 adults Protective effect of vaccination was similar for deep venous thrombosis and pulmonary embolism Conclusion of the study:
Influenza vaccination associated with reduced risk of VTE
Thromb Haemost. 2009 Dec;102(6):1259-64.
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Immunogenicity and reactogenicity in type I diabetes (9 30 years, n=53) Met CPMP requirement one month postvaccination:
High Seroprotection rates (>95%) for strains A/H1N1 and A/H3N2 Seroprotection of 70% in subunit vaccine for strain B Safe & adequately immunogenic against 3 influenza vaccine strains
Zuccotti et al., Long-lasting immunogenicity of a virosomal vaccine in older children and young adults with type I diabetes mellitus. Vaccine 2009 Aug 27;27(39):5357-62 Committee on Proprietary Medicinal Products (CPMP)
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Ghendon YZ, Kaira AN, Elshina GA, The effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly, Epidemiol Infect, 2006;134:718
Vaccination in asthmatic children is recommended Randomized double-blind placebo-controlled trial in 696 asthmatic children aged 6-18 yrs
Moderate beneficial effect on quality of life
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Bueving HJ Influenza vaccination in asthmatic children: effects on quality of life and symptoms. Eur Respir J. 2004; 24 (6): 925:931 Cates CJ, Jefferson TO, Bara AI, Rowe BH. Vaccines for preventing influenza in people with asthma (Cochrane review). Cochrane Database Syst Rev. 2004;(2):CD000364.
Randomized, three-arm, parallel group, multi-centre trial in 386 elderly subjects Immunogenicity & Safety of 3 vaccines:
Split Viron Vaccine MF59-adjuvanted subunit influenza vaccine Virosomal subunit influenza vaccine
Conclusion:
All have similar immunogenicity Virosomal subunit and Split Viron vaccines- less reactogenic than MF59-adjuvanted vaccine in elderly. Adjuvanted Vaccine not cleared for use in children and in pregnancy.
De Bruijn et al. Antibody induction by virosomal, MF59-adjuvanted, or conventional influenza vaccines in the elderly. Vaccine 2007; 26: 119-127.
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How does WHO determine which strains are put into influenza vaccine?
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an A/California/7/2009 (H1N1)-like virus 15 g HA/dose an A/Perth/16/2009 (H3N2)-like virus - 15 g HA/dose a B/Brisbane/60/2008-like virus - 15 g HA/dose
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Person aged > 65 years All children between 6 months to 8 years. Children age between 8 years to 18 years who receive long-term aspirin containing medications Adult and children with:
Chronic disorders such as HAD (Asthma), COPD, heart, renal, diabetes and people with immunodeficiencies.
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Flu vaccine may be considered from 2nd trimester of pregnancy. Administration of vaccine is recommended, irrespective of their stage of pregnancy in:
Pregnant women with medical conditions that increase risk of complications from influenza.
The American College of Obstetricians & Gynecologists and the American Academy of Family Physicians
Recommend routine vaccination of all pregnant women.
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Adults and Children from 36 months: 0.5 mL. Children from 6 to 35 months: 0.25 mL/0.5 mL limited clinical trial data. Children not previously vaccinated: 2nd dose given after 4 weeks interval. Route of administration: Intramuscular or deep subcutaneous injection.
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Influenza
Treatment
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Influenza treatment:
Antiviral drugs
Neuraminidase inhibitors
Zanamivir (inhalation) Oseltamivir
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Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.
Influenza treatment:
Antiviral drugs
Opportunity to impact viral replication with antiviral agents is limited Drug resistance
Limits use of antiviral agents
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Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th ed.
Influenza
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Influenza viruses cause disease among persons in all age groups . Rates of infection are highest among children.
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011 CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
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Why
need it?
Some persons can be infected with flu virus but have no symptoms. May pass on flu to someone else before you know you are sick, as well as while you are sick. It's worth considering for flu vaccine, even if you're young and healthy. Cost-Effectiveness:
Reduces health care, societal, productivity losses & absenteeism associated with flu illness.
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011 CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
Can the seasonal flu vaccine provide protection even if the vaccine is not a good match?
Antibodies created through vaccination with one strain of influenza viruses will often offer protection against related strains of influenza viruses. So even though circulating influenza viruses may drift or change from the time the vaccine composition is recommended, the vaccine may cross-protect against circulating viruses. The influenza vaccine contains three virus strains; so the vaccine would still protect against the other two viruses. This is particularly important in people at high risk for serious flurelated complications and for close contacts of high risk people.
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Flu has Significant morbidity and mortality. Vaccination decreases transmission of flu from caregivers and household contacts to persons at high risk.
CDC recommends:
Annual vaccination - all persons aged 6 months Children aged 6 months till 8 years to get 2 doses to provide adequate protection during first season.
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CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
Unexpected Benefits
Reduction in Streptococcus Pnemoniae cases. Reduction in Otitis Media. Benefit to Grandparents!
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France EK et al.
No increase in clinically important medically attended events during 2 weeks after inactivated influenza vaccination children aged <18 years.
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011 France EK, Glanz JM, Xu S, et al. Safety of the trivalent inactivated influenza vaccine among children: a population-based study. Arch Pediatr Adolesc Med 2004;158:10316
Why?
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011
Reasons
Exposed to one of influenza viruses in vaccine shortly before getting vaccinated. Ill from non-flu viruses. Weakened immune systems
Flu vaccine can still help prevent complications.
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011
Northern or Southern ?
Year round surveillance. Strains specific for Northern or Southern Hemisphere. Tropics as in India have 2 spikes of Flu season. No data yet.
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Influenza viruses continually undergo antigenic drift changes. Specific immunity persists from 6 to 12 months.
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CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
year?
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Euro surveillance , Volume 16, Issue 7, 17 February 2011. Surveillance and outbreak reports EFFECTIVENESS OF TRIVALENT SEASONAL AND MONOVALENT INFLUENZA A (H1N1) 2009. VACCINES IN POPULATION WITH MAJOR CHRONIC CONDITIONS OF NAVARRE, SPAIN: 2010/11. MID-SEASON ANALYSIS.
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0.25ml or 0.5ml ?
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TIV - recommended for high-risk children from 6 months of age. Effective in children at high risk of complications of flu including :
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Asthma & other chronic respiratory diseases, impaired immune response & cystic fibrosis.
Giezeman K. European Paediatrics, 2010;4: 2-8
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CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8]
Does immunity wane before end of season if vaccinated against seasonal flu early in season?
Flu vaccination provides protection against influenza strains through one influenza season. 90% of subjects have protective antibody titers by 2 weeks postvaccination. Vaccination can begin as soon as vaccine is available.
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011
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http://www.cdc.gov/flu/about/qa/misconceptions.htm. Accessed 09 August 2011
Conclusion
Influenza vaccination:
Overall considered best way to prevent infection & related complications Proved to be substantially efficacious in all studies:
Seroprotection rates met CPMP serological criteria for immunogenicity in all age group
Efficacy & safety in all target populations have been demonstrated by several studies & post-marketing surveillance.
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Please, please WASH hands with soap & water. And do a favor to your family and patients: And if sick with ILI, take rest till fever has gone!
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