Epidemiology of influenza in Ireland Lisa M. Domegan

1. Epidemiology of influenza in IrelandLisa M. Domegan

2. What is disease surveillance? • The continuing scrutiny of all aspects of the occurrence and spread of a disease that are relevant to its prevention. • Systematic collection, analysis, interpretation and dissemination of health data are essential.

3. Information for Action • Public Health Action • Priority Setting, • Planning, implementing, • and evaluating disease • investigation • control • prevention Surveillance Collection Analysis Interpretation Dissemination

4. Why is disease surveillance important? • Early detection & prevention of epidemics • Evaluate control & prevention measures • Monitor AMR • Early recognition of new infectious agents • Prioritising public health policy • Estim. magnitude of public health problem • Facilitate research • Detect changes in health practice

5. Disease surveillance ~ current issues in Ireland • Problems with current notification process • AMR • Enhanced surveillance of key diseases e.g. influenza, measles • Outbreaks ~ Norwalk like virus (winter vomiting disease), syphilis • Bioterrorism, SARS, Influenza pandemic planning • Infection control policy-noscomial infections e.g. respiratory syncytial virus (RSV) • CIDR ~ Computerised infectious disease reporting

6. Surveillance • Need to have both local and national surveillance • Local: Influenza outbreak in Naas School September 2003 • National: Influenza cases increasing on a national level October & November 2003 • Epidemiological study compliments microbiological study

7. Longer term surveillance • Provide data on temporal, demographic and geographic changes in infectious diseases • Demonstrates the requirement for intervention and the effectiveness of the intervention • Informs policy e.g. influenza pandemic planning • Monitoring and evaluation of immunisation programmes e.g. influenza vaccination uptake

8. Types of Surveillance • Active Vs Passive • Mandatory Vs Voluntary • Routine Vs Intensified • Sentinel/Local Vs National/International

9. Surveillance: General Principles Health Care System Public Health Authority Surveillance Data Information Control Decision Action

10. Surveillance: Basic Ingredients A good network of motivated people Clear case definition and reporting mechanism Efficient communication system Basic but sound epidemiological tools Good feedback and rapid response

11. Data flow model Peripheral Level Regional Intermediate Level bulletins PHD PHD National epi bulletin Central Level Electronic media NDSC FSA DOHC Eurosurveillance Regional Level Electronic media EU Networks WHO

12. Feedback

13. Community Network for the Epidemiological Surveillance and Control of Communicable Diseases (Decision 2119/98/EC)

14. Legal basis for the Community Network Amsterdam Treaty Article 152 Decision 2119/98/EC

15. Decision 2119/98/EC on the Community Network has two main objectives... Early warning and response system for the prevention and control of communicable diseases Epidemiological surveillance of communicable diseases

16. A. Diseases - Diseases preventable by vaccination - Sexually transmitted diseases - Viral hepatitis - Food- and water-borne diseases and diseases of environmental origin - Diseases transmitted by non-conventional agents - Air-borne diseases - Zoonoses - Serious imported diseases B. Special health issues - Nosocomial infections - Antimicrobial resistance PRIORITY LIST OF DISEASESCommission Decision 2000/96/EC

17. Influenza Surveillance

18. Aims of influenza surveillance • To reduce & monitor morbidity & mortality • To measure the impact of influenza activity • To identify if influenza is circulating, & if so determine which strain, type and subtype is present • To collate data over a number of influenza seasons to allow comparisons in the future of influenza activity levels. • Essential during a pandemic or interpandemic for planning of control measures

19. Structural properties of Influenza virus • Influenza virus is a single stranded RNA orthomyxovirus • Virions are irregularly shaped spherical particles, 80 –120 nm in diameter • Enveloped virus with 2 surface glycoproteins: Haemagglutinin and neuraminidase • Haemagglutinin ~ adherence and host cell entry • Neuraminidase ~ facilitates shedding of progeny virions from infected cells

20. Influenza types and subtypes • Influenza A, B & C • Influenza A can be classified into subtypes on the basis of the two surface glycoproteins • Influenza A • 15 subtypes of haemagglutinin H1-H15 • 9 subtypes of neuraminidase N1-N9 • All variations present in birds. Other reservoirs include pigs, horses, whales, humans.

21. Clinical illness by flu type • Influenza C rarely causes human illness • Influenza B clinical course changes little from year to year, milder than influenza A • Influenza A ~ major clinical importance due to morbidity & mortality associated with it. • Influenza A varies considerably and is responsible for epidemics and pandemics • Due to ability to readily change the structure of the surface glycoproteins.

22. Influenza clinical illness • Acute onset of fever, headache, myalgia, sore throat, coryza and a dry cough • Complications ~ Pulmonary complications (pneumonia), cardiac complications, rhabdomyolysis, encephalitis, transverse myelitis, Reye’s Syndrome • Spread primarily through aerosol droplet • Transmission also via contaminated environmental surfaces & hands • Incubation period ~ short 1-3 days • Age specific attack rates during an epidemic highest in school aged children

23. Clinical features of influenza

24. Impact of influenza • Mortality ~Death in 0.5 –1 per 1000 cases of influenza (mainly in those over 65) • In the UK, it is estimated that 3,000-4,000 excess deaths occur due to influenza infection per year. • >20,000 excess deaths occurred in 5 out of 23 influenza epidemics that occurred from 1972 to 1995. • > 90% of deaths occur in the elderly • >110,000 hospitalisations per year are due to influenza

25. Antigenic drift & shift • Minor changes can occur during viral replication known as “Antigenic drift”. These minor changes cause outbreaks or epidemics & are the reason why the influenza vaccine is reformulated annually • When major changes occur, a novel virus subtype is produced, this is known as “Antigenic shift”, & can result in a pandemic

26. Pandemic criteria (Nicholson et al): • Appearance in humans of a genetically new influenza virus • New influenza A subtype is not related to circulating viruses & could not have arisen from those viruses by mutation (Webster and Lever 1975) • Ability of virus to infect and cause disease in humans • A large susceptible population worldwide, lacking immunity to the new virus • A high % population infected & increased mortality rates.

27. Recent pandemics • 1918 “Spanish” H1N1, 1957 “Asian” H2N2, 1968 “Hong Kong” H3N2 • Influenza killed more people in a few months than all the armies of the 1914/1918 war in 4 years. • Deaths in hospitals exceeded 25% per night during the peak. • Origin of the 1918 pandemic is unknown..possibly China?…possibly America? • Spanish Flu of 1918 was by far the worst with 20-40 million deaths worldwide

28. Where? • 12 possible pandemics in last 400 years, point of origin is China/Russia/Asia. • Origin of pandemic influenza viruses is reassortment of human and avian viruses in pigs • Why China?: ¼ of worlds pop., ducks, pigs and humans live in close proximity and high density • 1957 & 1968 pandemics began in China • Reassortment viruses could arise anywhere!! When? • Mean time between last 4 pandemics was 25 yrs • Last pandemic was in 1968, 35 years ago!!

29. WHO Influenza programme • 110 National Influenza centres in 83 countries (of which NVRL is one) • Early influenza isolates must be subtyped in house and then sent to WHO headquarters for confirmation • Subtyping information allows immediate identification of new strains and appropriate vaccine preparation

30. Influenza surveillance in Ireland • Fourth year of influenza surveillance in Ireland • NDSC in collaboration with ICGP & NVRL • Surveillance involves two aspects:clinical & virological data • Clinical data provides epidemiological features & the impact of influenza infection • Virological data confirmsinfluenza is circulating, identifies strains, monitors for the emergence of novel viruses

31. Sources of data • Sentinel GPs ~ influenza-like illness (ILI) • National Virus Reference Laboratory (NVRL) ~ Confirmed cases of influenza • Absenteeism levels in sentinel schools • Total, A & E & respiratory admissions in sentinel hospitals • Departments of Public Health ~ influenza activity regionally

32. Sentinel general practices • 35 sentinel general practices reporton the number of patients with influenza-like illness (ILI) per week “Sudden onset of symptoms with temperature of380C or more with at least two of the following: headache, myalgia, dry cough, sore throat in the absence of any other disease” • Patients were those attending for the first time • 35 practices include 66 practitioners

33. Sentinel general practices • Sentinel GPs cover 2.8% of the population • Location based on population of each health board • Recruitment based on enthusiasm for project & competence at using software package • Sentinel GPs belong to two computer software user groups, Health One & GP Clinical

34. Virological surveillance • Sentinel GPs send combined nasal & throat swabs on suspected cases of ILI per week to NVRL. • Samples undergo both cell culture and polymerase chain reaction testing. • Antigenic characterisation in WHO influenza laboratory, Millhill • Hospital respiratory samples referred to NVRL

35. Growth of flu virus in embryonated eggs

36. Growth of flu virus in embryonated eggs

37. Important considerations for growth of influenza in cell culture • Specimen type • Cell line - MDCK cells (Madin-Darby canine kidney) • rapid versus traditional culture assays • rapid:- direct antigen detection, shell vial 1-3 days • traditional :- 5-14 days • proteolytic activation of virus • identification of virus growth • cytopathic effect • haemagglutination • immunofluoresence

38. Molecular diagnosis of influenza infection • Detection of viral nucleic acid RNA • amplification technology:- RT-PCR • Advantages • can identify non-viable virus • specific (identification of a sequence only found in flu viral genome) • subtyping of virus • multiplexing • Disadvantages • contamination • no virus isolated

39. Regional influenza surveillance • Departments of Public Health selected 10 sentinel hospitals, 1 in each Health Board • Sentinel hospitals report weekly total admissions, total A/E admissions & total respiratory admissions • 1y & 2y sentinel schoolsreport weekly, on daily absenteeism numbers • Located in close vicinity to sentinel general practices

40. Regional influenza surveillance • Departments of Public Health send a weekly influenza activity index to NDSC • Index based on sentinel ILI consultation rates, laboratory confirmed cases of influenza, sentinel hospital & school data • Map of influenza activity by health board included in weekly surveillance report

41. Weekly Report ~ NDSC • NDSC collates & analyses the data • Weekly influenza surveillance report between October-May • Results of clinical & virological data reported, map of influenza activity, summary of influenza activity worldwide. • Report emailed to participants involved in influenza surveillance & posted on NDSC website www.ndsc.ie

42. 2000/2001 influenza season in Ireland Key Points • Peak incidence occurred during late Feb/early Mar 2001 • The peak age specific consultation rate was in 15-44 year age group • Influenza B 60.7% of positive swabs & influenza A for 39%. • Predominant influenza A subtype A (H1N1)

43. 2001/2002 influenza season in Ireland Key Points • Activity mild, peaking in Feb 2002 • Peak age specific consultation rate in 15-44 year age group • Influenza A (H3N2) predominant circulating strain • New strain announced by WHO, influenza A (H1N2) • New strain identified in Ireland

44. Influenza A (H1N2) • Feb 2002, WHO announced new strain influenza A (H1N2) • Genetic reassortment of genes in H1N1 & H3N2 • During 2001/2002 A (H1N2) isolated in Ireland, England, Scotland, France, Israel, Egypt, US and Canada • Previously detected in China in 1988/89, not in humans • Vaccinees should have good level of immunity • No unusual clinical symptoms & no increase in mortality

45. Influenza A (H1N2) in Ireland • Identification of H1N2 highlights effectiveness of surveillance system • 15 influenza A (H1N2) viruses detected in Ireland • Accounted for 23.1% of all positive specimens • 11/15 cases were aged between 9 and 19 • 9/9 cases were not vaccinated

46. Influenza activity worldwide 2001/2002 • Europe & US mild to moderate activity: A (H3N2) predominating • A (H1N2) identified ~ school outbreaks in UK • B/Victoria-like viruses detected this season; first time since 1991 in Asia • B/Hong Kong-like viruses detected in Canada • 2001/2002 vaccine ~ limited protection to B/Victoria-like & B/Hong Kong-like viruses • Avian influenza A (H5N1) in Hong Kong farms/markets ~ chickens culled & first chicken vaccination programme

47. 2002/2003 influenza season in Ireland Key Points • Influenza activity mild, peaking in Feb 2003. • 347 ILI cases reported by sentinel GPs • Peak age specific consultation rate in 10-14 year age group, coinciding with influenza B increase & increased sentinel school absenteeism associated with ILI. • Influenza B predominant circulating strain.

48. GP consultation rate for ILI per 100,000 population by report week for the 2000/2001, 2001/2002 & 2002/2003 influenza seasons

49. Age and sex specific ILI rate per 100,000 population, 2002/2003 season

50. Number & percentage of influenza virus detections, 2002/2003 season