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Influenza – Vaccine

Influenza – Vaccine. Pope Kosalaraksa Department of Pediatrics Faculty of Medicine Khon Kaen University. Influenza Pandemics in 20th Century. Credit: US National Museum of Health and Medicine. 1918: “Spanish Flu”. 1957: “Asian Flu”. 1968: “Hong Kong Flu ”. 1 - 4 million deaths.

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Influenza – Vaccine

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  1. Influenza – Vaccine Pope Kosalaraksa Department of Pediatrics Faculty of Medicine Khon Kaen University

  2. Influenza Pandemics in 20th Century Credit: US National Museum of Health and Medicine 1918: “Spanish Flu” 1957: “Asian Flu” 1968: “Hong KongFlu” 1 - 4 million deaths 20 - 40 million deaths 1 - 4 million deaths A(H3N2) A(H1N1) A(H2N2) Source: Meslin / WHO

  3. Eras of Human Influenza Viruses A(H1N1) A(H1N1) Russian Flu Spanish Flu A(H3N2) A(H3N8) Hong Kong Flu A(H2N2) A(H2N8) Asian Flu Type B 1968 1889 1918 1957 1977 2005

  4. Influenza • Virus infection • Occurs worldwide • Repeated infections throughout life • Outbreaks every year • regular epidemics • occasional pandemics • Usually seasonal winter illness in temperate climates, less seasonal in tropics

  5. Seasonality of Influenza J F M A M J J A S O N D Northern temperate Tropics Southern temperate

  6. Influenza Virus - Schematic Haemagglutinin Spikes Neuraminidase Lipid Envelope Internal Proteins H N Single stranded RNA genome (Ribonucleoprotein) as 8 separate pieces Highly mutable can undergo genetic reassortment

  7. Influenza A (subtypes) Influenza B H1N1 H2N2 Human Influenza Viruses

  8. Antigenic Variation Antigenic Drift • gradual change in surface antigens • occurs for both influenza A & B • due to mutations (in HA and NA) • results in annual outbreaks and epidemics Antigenic Shift • sudden change • occurs only for influenza A • explosive spread - pandemics

  9. Influenza in Other Species

  10. เชื้อกลายพันธุ์ในคน(Reassortment in human) การระบาดใหญ่ (Pandemic) นกอพยพ นกน้ำ ไก่ สัตว์ปีกที่เลี้ยงไว้ Source: WHO/WPRO 13 Sep 04

  11. เชื้อกลายพันธุ์ในสุกร(Reassortment in pigs) นกอพยพ นกน้ำ ไก่ สัตว์ปีกที่เลี้ยงไว้ Source: WHO/WPRO 5 Oct 04

  12. Full influenza strain analysis requires virus isolation MDCK cell culture (Madin Darby canine kidney) or embryonated chicken eggs

  13. Naming of Human Influenza Viruses All viruses grown in the laboratory receive a designation: Type / Location / sequential number / year eg. A / Sydney / 20 / 2004 eg. A / Goose / Hong Kong / 437 / 99 (H5N1)

  14. Patients with High-Risk of Complication from Influenza 1. Elderly (> 65 y.) 2. Children with CHD, CPD, asthma immumosuppression, HIV/AIDS, Cancer 3. Children with long term aspirin 4. Infant from 0-24 months

  15. Influenza Infection and Illness Rates Houston Family Study, 1976-1984 Rate Per 100 Persons <2 2-5 6-10 11-17 18-24 25-34 > 35 Age (years) Glezen et al: Pediatr Infect Dis J 1997; 16:1065-8.

  16. Hospitalization Rates in “High Risk” and “Low Risk” Populations Number High-Risk Low-Risk 200 150 100 50 0 <1 1 - <5 5 - <15 15 - 44 45 - 64 >65 Age (years) Glezen et al. Am Rev Respir Dis 1987;155(6):1119-1126; Neuzil et al. NEJM 2000;342:225-231; Neuzil et al. J Pediatr 2000;137:856-864.

  17. Shedding of Wild-type Virus Onset Onset SARS Influenza - adult -1 0 5 7 14 d 0 7 14 d Onset Onset Influenza - children Influenza – young children -1 0 7 10 14 d -6 0 7 10 14 d

  18. Clinical Manifestations 1. “Classic” - abrupt fever, chill, cough rhinorrhea, sore throat, myalgia, headache, anorexia (sensitivity = 63-78% ; specificity 55-71%) 2. “Nonspecific” - croup, bronchiolitis - conjunctivitis - acute gastroenteritis - sepsis-like syndrome - acute febrile illness

  19. Common manifestations of influenza illness in children Age Manifestations Frequency Infant, toddler Afebrile URI + <5 yr oldFebrile URI +++ Acute otitis media ++ Pneumonia + Croup + Bronchiolitis + “Sepsis syndrome” +

  20. Common manifestations of influenza illness in children Age Manifestations Frequency Child Afebrile URI + >5 yr old Flu-like syndrome* +++ Acute otitis media ++ Pneumonia + Myositis + Myocarditis rare Encephalopathy rare *Fever,cough,headache,myalgia,malaise

  21. Complications of Influenza Illness 1. AOM occur > 20% of children < 6 y.o. with influenza (2/3 bacterial superimposed) 2. Exacerbation of asthma, chronic lung conditions 3. Pneumonia, bronchiolitis occur 25% children with influenza 4. Myositis 5. Myocarditis, cardiomyopathy 6. Encephalitis, GBS 7. Reye syndrome

  22. Fig.2 Reported Cases of Influenza by Month, Thailand, 1997-2001

  23. Influenza vaccines • Inactivated or killed vaccine : whole virus - H, N, internal Ag, lipid : split virion - H, N, external Ag, internal Ag : subunit - H, N • Live attenuated vaccine

  24. Influenza Vaccination: Protection Against Hospitalisation and Death Influenza-like illness diagnosed clinically Outpatient visits for pneumonia and influenza Hospitalizations for all respiratory conditions Hospitalizations for strokes Hospitalizations for influenza and pneubmonia Hospitalizations for cardiac events Mortality following hospitalizations for influenza and pneumonia Mortality from all causes 0 20 40 60 80 100 Influenza Vaccine Effectiveness Vu T et al., Vaccine 2002: 20;1831-6 Nichol et al., NEJM 2003: 348; 1322-32

  25. The Global Distribution of Influenza Vaccine, 2000 - 2003 Africa, East Med SE Asia 0.25 291.9 270.5 256.7 W Pacific 230.9 61.1 29.9 Americas Doses disstributed (millions) Europe

  26. Influenza Vaccine Use in 50 Countries 2002 AUSNZ Korea Japan Taipei HK SAR Van Essen GA etal. Vaccine 2003; 21;1780-5

  27. Hong Kong Singapore Japan Australia New Zealand Rep. of Korea Taipei Czech Rep. Argentina Hungary Slovak Rep. Chile Uruguay Malaysia Estonia Mexico Poland Croatia Brazil Russian Rep. Lithuania Columbia Costa Rica Latvia Romania Thailand Bulgaria Philippines China Indonesia Economic Development and Influenza Vaccination in the Western Pacific, Latin America and Central & Eastern Europe in 2000 0 100 150 200 50 25,000 20,000 15,000 10,000 5,000 0 Gross domestic product ($ PPP) Influenza vaccine distribution (doses/1000 population) Fedson et al. Options V 2003

  28. What are the issues for influenza vaccine use in Asia? • Recognised that influenza vaccination is beneficial in most age groups …… • Why are influenza vaccines not used in all countries? • Are minimal resources an issue? • Is it a lack of knowledge of the burden of disease • just not a priority?

  29. Low coverage in Thialand • Low awareness : diagnosis • Reactogenicity : fever, pain, myalgia • Cost • administration annually • Low mortality

  30. Avian Influenza

  31. Influenza vaccine • Avian flu prevention ?

  32. Influenza vaccine • Avian flu prevention ? • Influenza vaccine : prevent human influenza infection : co-infection : reassortment : new strain, no immunity : pandemics

  33. Northern or Southern strain

  34. Recent Vaccine Formulations WHO Recommendation for 2005 Southern Winter: an A/New Caledonia/20/99 (H1N1)-like strain an A/Wellington/1/2004 (H3N2)-like strain a B/Shanghai/361/2002-like strain WHO Recommendation for 2005-6 Northern Winter: an A/New Caledonia/20/99 (H1N1)-like strain an A/California/7/2004 (H3N2)-like strain a B/Shanghai/361/2002-like strain

  35. Vaccine schedule * Intramuscular

  36. Should we give influenza vaccine to our children? • Incidence high • Severity vary • Safety some complications • Feasibility IM / intranasal • Acceptibility poor • Cost moderate • Budget preparedness • Selective groups • Prevent pandemics

  37. Human infections, contracted from animals, no man-to-man Tx Human cases, from man-to-man Tx, limited scale Extended epidemic in the country Pandemic New influenza virus found in animals Phases in pandemic development (simplified version)

  38. Projected impact of influenza pandemic inThailand Cases 26,000,000 Deaths 260,000 – 2.6 mill. Current CFR of H5N1 avian influenza: 70% Cases 6,500,000 deaths 65,000- 650,000 Extensive social and economic impacts Cases rate 10% CFR 1 - 10% Case rate 40% CFR 1 - 10% คาดการณ์ขั้นสูง คาดการณ์ขั้นต่ำ

  39. Influenza Foundation (Thailand) 2004Available on URL: http://www.ift2004.org

  40. Common problems in vaccination

  41. Common problems in vaccination 1. หากเด็กไม่มารับวัคซีนตามที่กำหนด ควรให้วัคซีนที่ขาดไปอย่างไร 2. ระยะห่างระหว่างวัคซีนแต่ละครั้ง สามารถเลื่อนได้มากน้อยเพียงใด

  42. ระยะห่างระหว่างวัคซีนแต่ละเข็มระยะห่างระหว่างวัคซีนแต่ละเข็ม หมายเหตุ * วัคซีน DTP เข็มที่ 5 ไม่จำเป็น ถ้าเข็มที่ 4 ให้หลังอายุ 4 ปี หลังจากนั้นกระตุ้นด้วย dT ทุก 10 ปี ** วัคซีนฮิบ ถ้าเริ่มฉีดหลังอายุ 6-12 เดือน ฉีด 2 เข็ม ถ้าเริ่มเข็มเดียว

  43. Common problems in vaccination 3. การฉีดวัคซีนแต่ละครั้ง สามารถฉีดได้มากที่สุดกี่เข็ม 4. เราสามารถผสมวัคซีนหลายอย่างในเข็มเดียวกันได้หรือไม่

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