General Issues of Influenza

1. General Issues of Influenza Updated: 26 February 2009

2. Learning Objectives Differentiate between the Influenza A, B and C Describe characteristics of antigenic drift and shift List avian influenza control measures in poultry populations Describe measures to mitigate risk for poultry and outbreak response workers

3. Contents • Influenza background • Influenza classification • Seasonal influenza • Avian influenza • Pandemic influenza

4. Background • The origin of the word "Influenza" dates from times when astrologers explained disease causation by the unfavourable influence of the stars • In Italian "sul l'influenza delle stellini" means under the influence of the stars. • "Fowl-plague" (Avian Influenza) was identified over 100 years ago, in Italy, but not discovered to be an influenza A virus until 1955 • Human influenza was not discovered to be a virus until 1933, 15 years after the 1918 pandemic.

5. Classification • There are 3 types of influenza virus: A, B and C • Influenza A can infect many species (birds, humans, pigs, horses, etc.) • Wild aquatic and shore birds are the natural reservoir for influenza A viruses • Influenza B + C primarily infects humans

6. Influenza Type A • Causes epidemics and pandemics • There are multiple "sub-types" of influenza A characterized by the type of two surface glyco-proteins: • Haemagglutinin (HA) = 16 types • Neuraminidase (NA) = 9 types • All influenza A subtypes circulate in wild birds • Humans can be infected with Influenza A

7. Influenza Virus Asurface glyco-proteins Haemagglutinin (HA) 16 Types Neuraminidase (NA) 9 Types

8. N1 H1 N2 H2 N3 H3 N4 H4 H5 N5 H6 N6 H7 N7 H8 N8 H9 N9 H10 H11 H12 H13 H14 H15,16 Species Infected by Influenza A, HA and NA Subtypes

9. Influenza Type B and C • Type B (primarily infects humans) • Is not sub-typed • Can cause epidemics but less severe than A • Is responsible for substantial outbreaks every two - three years • Has not caused pandemics • Type C causes mild illness in humans and does not cause epidemics or pandemics

10. DIRECT Mechanisms of Influenza Virus Antigenic “Shift” 16 HAs 9 NAs Non-human virus Human virus Reassortant virus

11. Antigenic Drift vs Antigenic Shift Antigenic DRIFT • Minor change in HA / NA • Point mutations during replication, but subtype remains the same • Continuous changes, so virus continues to cause illness and deaths • Limited partial immunity may exist to changed virus • Results in the need to update vaccines annually Antigenic SHIFT • Major change in HA / NA • New subtype introduced • Caused by genetic re-assortment when 2 subtypes infect a host simultaneously OR • Caused by direct transmission from birds or other animals to humans

12. Seasonal Influenza • The small changes - same subtype - Antigenic drift – are the cause of epidemic seasonal influenza • Seasonal influenza viruses • Are a public health problem every year • Circulate throughout the human population • Spread easily from person to person • The severity (morbidity + mortality) of seasonal influenza varies from year to year

13. Seasonal Influenza • Populations develop immunity to the previous season's viruses • Varying seasonal severity reflects: • the ability of pre-existing immunity to combat a changed virus • the increasing level of immunity to a changed virus over seasons • differences in viral virulence (ability to cause disease and complications)

14. Seasonal Influenza Spread • Primarily contracted from respiratory droplets • Coughing, sneezing, talking • Or touching contaminated objects, people or self contamination with own hand, then touching nose and eyes without washing hands

15. Symptoms of Seasonal Influenza • Systemic and respiratory complaints • common complains • fatigue • muscle aches headache • Fever • sore throat • Cough • runny nose

16. Course of Seasonal Influenza • Incubation on average is 2 days (range 1 – 5) • Person may be infectious from 1 day before until 5 days after onset of symptoms, children potentially longer • Generally a self-limiting condition of about one week • BUT may cause serious medical complications and death

17. Seasonal Influenza Excess morbidity and mortality • Influenza is highly contagious • 5% – 20% of population annually contract seasonal influenza • generally young, elderly and chronically ill most severely effected • Substantial economic impact from absenteeism, morbidity, mortality and medical costs • increased medical consultations, hospital admissions and mortality

18. Seasonal Influenza Prevention & Control • Pharmaceutical: • Vaccine • Currently the best prevention • Effectiveness depends on composition and circulating strain • Expensive • Strain selection needs to be revised yearly • Antivirals • Non-pharmaceutical: • Social distancing • Respiratory hygiene

19. WHO Global Influenza Network • Since 1947 WHO has established and coordinated a global human influenza surveillance network consisting of • > 120 laboratories, in > 90 countries • 5 collaborating centres • Collect samples and detect influenza virus changes • Prepare candidate vaccine strains and distribute to vaccine producers bi-annually in both hemispheres

20. WHO Global Influenza Network

21. Human Seasonal Influenza Vaccine • Only 300 million influenza vaccine doses (<5% global population) produced annually from eggs • Strains made available from WHO Global Surveillance Network • Production and consumption highly localized • >95% produced in nine countries (>65% in Europe) • 12% of population use 62% of vaccine • Production matches demand (i.e. market driven) • Very little surge capacity, needs lead time of at least six months • increased seasonal demand enhances surge capacity

22. Avian Influenza in Birds • "Fowl-plague" (Avian Influenza) first identified over 100 years ago during an outbreak in Italy • 1955 identified as Influenza A virus • Since then, disease has occurred mostly in birds at irregular intervals in all world regions • FAO (Food and agriculture Organization) and OIE (World Organization for Animal health) are lead UN agencies combating disease in animals

23. Avian Influenza in Birds • All avian influenza viruses are A – subtypes • Are highly contagious in birds • Wild birds are often asymptomatic carriers • Domesticated populations (chickens, ducks, turkeys) become infected by contact with wild birds • Avian infection can cause 2 distinct forms of disease: • Low pathogenic avian influenza ( LPAI) • Highly pathogenic avian influenza (HPAI)

24. Low and High PathogenicityAvian Influenza in Birds • Low - pathogenic avian influenza (LPAI) • May go undetected • Or result in mild symptoms • Ruffled feathers • Reduced egg production • High - pathogenic avian influenza (HPAI) • Rapid spread, effecting multiple organs • Mortality rate 90 -100% within 48 hours

25. H5N1 • H5N1 is a novel avian influenza A-subtype that: • Has caused a global epi-zootic • Causes asymptomatic, high and low pathogenic forms of disease in wild birds • From media coverage has become synonymous with the terms "avian influenza" and "bird flu" • Has crossed the species barrier and, so far, caused limited human disease usually resulting from close or direct contact with infected birds or possibly contaminated surfaces

26. Avian influenza (AI)- Concerns • Any new, or re-assorted AI subtype, including H5N1, could have significant implications for • Agriculture • Society • Economies • Public Health • Affecting every strata of society at • Individual • National and • International levels

27. Examples of Economic Impact • Vietnam • 75% rural households raise backyard flocks • Chickens are important source of protein and revenue • One chicken = 700% return on investment (FAO • Average rural flock size = 16 chicken • Thailand • Globally 3rd largest poultry exporter prior to H5N1 • Exports worth $1 billion US (~1.5% of GDP) • Prevention and control costs • Culling, compensation, poultry vaccination

28. Economic Impact • Emergence of a pandemic strain will cause a significant down turn in the global economy • It will disrupt availability of essential stocks • SARS lasted 3 months and affected <800 people • SE Asia GDP was reduced by 2% for that period (US$18bio) US$2 mio per patient

29. Combating H5N1 • Control of AI is a complex task requiring multisectoral cooperation • National government strategies should include both animal and public health dimensions • International assistance for AI response is coordinated by FAO and OIE with WHO contributing to the public health components • The overarching goal is eradication • Strategies may differ in endemic countries and those experiencing the first outbreak

30. Combating H5N1 • Important considerations are to reduce the • quantity of virus circulation in poultry • opportunity for human infection • To achieve this requires • Knowledge of the major pathways of spread • A coordinated approach using multiple strategies

31. Multiple Strategies Required • Effective surveillance for outbreak detection and reporting • Improved bio-security on farms • Controlled movement of birds and products • Changes in agricultural, industrial and social practices • Culling and disposal of carcasses • Proper use of vaccination • Social mobilization and communication

32. Influenza A/H5N1 virus: Survival and inactivation • Virus can be present in infected poultry in all organs and parts of the bird • Survival in faeces: • 35 days at 4°C/6 days at 37°C • Survival in poultry houses: • Several weeks • Only thorough cooking will effectively inactivate the virus • freezing and refrigeration not adequate • Eggs from infected animals can be contaminated on the outside and inside of the shell

33. Possible Modes of AI Transmission • From infected animals to humans • Contact with respiratory secretions, faeces • contaminated feathers, blood from infected birds • Contact with contaminated surfaces • Raw food consumption (?)

34. Identified Risks for AI Transmission to Humans • Direct contact with poultry: • Home slaughtering • Handling, cooking and consumption of diseased chicken and ducks • Presence of diseased and dead chickens in oraround the house • Playing around diseased/dead chickens • Consumption of raw duck blood • In some affected regions increased risk due to: • Up to 80% of poultry raised at the household level • Marketing of live poultry directly to consumers and on-site slaughtering ("live bird markets" or "wet markets") • Small scale, decentralized or home-slaughtering

35. Perspectives • Number of human cases are still limited compared to high contact rate. • No reassortment between human virus A/H3N2 and avian A/H5N1 detected so far. • Control of animal infections will be long, difficult and costly. • Continuous circulation of virus in animal populations imply continuous risk for further human infections and thus an increased risk of a pandemic due to A/H5N1

36. Recommendations to reduce exposure to the AI virus through food: • Separate raw meat from cooked or ready-to-eat foods to avoid contamination. • Keep clean and wash your hands. After handling raw chicken or eggs, wash your hands thoroughly with soap. Wash and disinfect all surfaces and utensils that have been in contact with the raw meat. • Cook thoroughly. Either ensure that the poultry meat reaches 70°C at the centre ("piping” hot) or that the meat is not pink in any part. Egg yolks should not be runny or liquid. • Do not eat raw poultry parts or raw eggs.

37. Available in 39 languageswww.who.int/foodsafety/ consumer/5keys/en/

38. Requirements for a Pandemic Global outbreak of disease • New influenza A virus emerges in humans • Minimal or no population immunity • Causes serious illness; high morbidity/mortality • Spreads easily from person to person Photo provided by CDC

39. Seasonal vs Pandemic Influenza Seasonal Influenza • A public health problem each year • Usually some immunity built up from previous exposures to the same subtype • Infants and elderly most at risk • Result of Antigenic Drift Pandemic Influenza • Appear in the human population rarely and unpredictably • Human population lacks any immunity • All age groups, including healthy young adults, may be at increased risk for serious complications • Result of Antigenic Shift

40. Pandemic Infuenza Concerns • Historical precedent • 20th century experience 1918, 1957, 1968 • Unpredictable • Next pandemic is anticipated, but timing, duration and severity cannot be predicted • Potential for rapid global spread within months • No pandemic vaccine commercially available • Potential to kill millions (all age groups) – attack rate and case fatality rate dependent • Stress on social, health and economic systems

41. Mortality comparisons

42. Developed by The Global Influenza Programme o the World Health Organization with the assistance of: • Department of Epidemic and Pandemic Alert and Response • WHO/Food safety, zoonosis and foodborne diseases • Centres for disease control and prevention • Health Canada • European Centre for Disease prevention and Control • WHO/regional offices • WHO/Indonesia country office