Influenza

1. Influenza Prof / Mohamed AwadTageldin 2014

2. Influenza Updated

3. From November through December 2013, CDC has received a number of reports of severe respiratory illness among young and middle-aged adults, many of whom were infected with influenza A (H1N1) pdm09 (pH1N1) virus. Multiple pH1N1-associated hospitalizations, including many requiring intensive care unit (ICU) admission, and some fatalities have been reported. The pH1N1 virus that emerged in 2009 caused more illness in children and young adults, compared to older adults, although severe illness was seen in all age groups. While it is not possible to predict which influenza viruses will predominate during the entire 2013-14 influenza season, pH1N1 has been the predominant circulating virus so far. For the 2013-14 season, if pH1N1 virus continues to circulate widely, illness that disproportionately affects young and middle-aged adults may occur.

4. Seasonal influenza contributes to substantial morbidity and mortality each year in the United States. In the 2012-13 influenza season, CDC estimates that there were approximately 380,000 influenza-associated hospitalizations • Although influenza activity nationally is currently at low levels, some areas of the United States are already experiencing high activity, and influenza activity is expected to increase during the next few weeks.

5. The spectrum of illness observed thus far in the 2013-14 season has ranged from mild to severe and is consistent with that of other influenza seasons. While CDC has not detected any significant changes in pH1N1 viruses that would suggest increased virulence or transmissibility, the agency is continuing to monitor for antigenic and genetic changes in circulating viruses, as well as watching morbidity and mortality surveillance systems that might indicate increased severity from pH1N1 virus infection. In addition, CDC is actively collaborating with state and local health departments in investigation and control efforts.

6. End of January 2014 Summary • In North America influenza activity remained high in recent weeks with A(H1N1)pdm09 predominant. • In Europe, a slight increase in influenza activity has been observed, which may indicate the start of the influenza season. • In China influenza activity continued to increase with influenza (H1N1)pdm09, A(H3N2) and influenza B co-circulating. • In the southern hemisphere influenza activity remained low. • In countries of tropical areas variable influenza activity was reported. • Based on FluNet reporting (as of 23January 2014, 13:25 UTC), during weeks 1 to 2 (29 December 2013 to 11 January 2014), National Influenza Centres (NICs) and other national influenza laboratories from 72 countries, areas or territories reported data. The WHO GISRS laboratories tested more than 81 261 specimens. 24 494 were positive for influenza viruses, of which 22 425 (91.6%) were typed as influenza A and 2069 (8.4%) as influenza B. Of the sub-typed influenza A viruses, 11 033 (80.5%) were influenza A(H1N1)pdm09 and 2669 (19.5%) were influenza A(H3N2). Of the characterized B viruses, 220 (84%) belonged to the B-Yamagata lineage and 42 (16%) to the B-Victoria lineage.

7. Northern Africa and the Western and Central Asia region • In Central and Western Asia, increased influenza A(H3N2) activity was reported from Islamic Republic of Iran and Turkey in beginning of January. Egypt experienced an increase in A(H1N1)pdm09 activity, and Turkey experienced increases of A(H3N2) activity. Influenza activity remained low in the remainder of the region.

8. Influenza

9. Influenza • Highly infectious viral illness • Epidemics reported since 16th century • Virus first isolated in 1933

10. Signs and Symptoms • Influenza is an acute, viral respiratory infection. • Fever, chills, headache, aches and pains throughout the body, sore throat which may lead to bronchitis or pneumonia. • Vomiting and diarrhoea may also occur. • Many deaths have been attributed to influenza

11. CommonSymptoms • • Respiratory disease • Abrupt onset of symptoms • Fever (up to 104° F) • • Chills (sometimes shaking) • • Muscle aches and pains • • Sweating • • Dry Cough • • Nasal congestion • • Sore throat • • Headache • • Malaise • • Fatigue

12. Burden of Influenza • 10% to 20% of the population is infected with influenza virus each year • Average of more than 200,000 excess hospitalizations each year • Persons 65 and older and 2 years and younger at highest risk • Average of 36,000 deaths each year • Persons 65 and older at highest risk of death

13. Hospitalization Rates for Influenza By Age and Risk Group* Rate** (high-risk) 808 471 231 92 62 318 507 Rate** (not high-risk) 274 72 39 23 16 22 182 Age Group 0-11 mos 1-2 yrs 3-4 yrs 5-14 yrs 15-44 yrs 45-64 yrs >65 yrs * Data from several studies 1972 - 2004 * Hospitalizations per 100,000 population

14. Influenza: Who’s at risk? • Everybody • People with greater risk: • ≥ 65 years old • Patients with chronic diseases • Asthma/Lung chronic disease • Chronic Heart Disease • ≤ 5 years old

15. Influenza Pandemics • A pandemic is a world wide spread of infection occurring in many countries simultaneously. • Flu pandemics occur approximately every thirty years. • Flu pandemics occur because a new strain of the virus emerges for which people have no immunity and there are no vaccines available.

16. Pandemics • New flu viruses occur due to mutation • Mutation occurs because different strains of influenza virus can exchange genes by infecting different animals • Avian influenza viruses can exchange genes with human influenza viruses creating hybrid strains

17. 1918 - 1919 pandemic • This killed between 20 – 40 million people • Face masks were worn but provided little protection against infection

18. Cause • The cause of influenza is the influenza virus. • Influenza A, B and C viruses are found • Influenza A viruses are associated with serious illness and pandemics

19. Influenza virus • The flu virus is an RNA virus • The genome codes for five viral proteins and is made of eight fragments. • The virus has a lipid envelope with two glycoproteins present

20. INFLUENZA VIRUS • Family: Orthomyxoviridae • Negative sense single strand RNA genome • Genus: Influenza A, B • Eight segments • Genus: Influenza C • Seven segments • Genus: (unnamed, Thogoto-like viruses) • Seven segments • Genus: (unnamed, Infectious Salmon Anemia virus) • Seven segments

21. 2-6Gal 2-3Gal • Influenza A virus • Family: Orthomyxoviridae • Segmented negative sense single strand RNA genome HA NA PB1, PB2, PA NP M1 NEP www.cdc.gov M2 NS1, PB1-F2 Infected cells

22. Type A influenza cannot be eradicated 16 HA subtypes 9 NA subtypes a2-6Gal a2-3Gal a2-3Gal a2-6Gal a2-3Gal a2-6Gal

23. Influenza types Type A Potentially severe illness Epidemics and pandemics Rapidly changing Type B Usually less severe illness Epidemics More uniform Type C Usually mild or asymptomatic illness Minimal public health impact Centers for Disease Control and Prevention. Influenza Prevention and Control. Influenza. Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.

24. Flu virus glycoproteins • Haemagglutinin - this glycoprotein plays a part in infection and provides the “H” in the strain type. • Haemagglutinin attaches the virus to cells and allows the viral envelope to fuse with the cell membrane and enter cells. • Neuraminidase – has a mushroom shape, its role is to allow the release of viruses to infect other cells

25. HN terminolgy • H refers to Haemagglutinin types and each is given a number H1, H2 etc, • Neuraminidase is designated N and different forms are available as well e.g. H5N1 (avian) and H1N1. • Different combinations of H and N glycoproteins give rise to different strains

26. Antigenic shift and antigenic drift • Mutations which produce small changes in antigens are referred to as antigenic drift and these occur in the same strain • Mutations which result in a major change and produce new strains are referred to as antigenic shifts

27. Transmission • The virus is spread by inhalation or by direct contact. • Reservoirs of infection are primarily humans, but birds and pigs can act as reservoirs. • The multiple host status makes for mixing of flu types.

28. Influenza: Transmission • Incubationperiod: 1-4 days, average 2 days • Transmissionmaystart 1 or 2 daysbeforeonset of symptoms and lastfor a week • Immunocompromisedpatientsmaytransmitthe virus for up to a monthafteronset of symptoms • Virus particles spread throughcoughing and sneezing • Oneinfectiousparticle can generate up to 1,000 virus particles

29. Prevention • Public education campaigns are used to reduce infection rates • Isolation of infected people is desirable but not always practical • Immunisation

30. Immunisation • Vaccines are offered to people aged 65 or over (Note: Currently this group has some immunity and are not being targeted) • Clinically at risk groups – asthmatics, immuno-compromised patients, diabetics, people with chronic respiratory disease. • Health care workers • Vaccine effectiveness varies between 40 – 60%

31. Influenza Prevention • Vaccination before the start of influenza season • Northern Hemisphere: October-November • Southern Hemisphere: April-May • Antiviral treatment • Therapeutic • Prophylactic

32. Viral immunity - Vaccines

33. Viral immunity - Vaccines • Infection: solid immunity to homologous virus • Antibody to surface genes; HA and NA • CTL: peptides from internal proteins • Two circulating subtypes: H1N1 and H3N2 • H3N2 more important in morbidity and mortality • Inactivated virus vaccines • Safe and generally efficacious • Live attenuated vaccines (FluMist®) • Safe and generally efficacious

34. Influenza Vaccines • Inactivated subunit (TIV) • Intramuscular • Trivalent • Annual • Live attenuated vaccine (LAIV) • Intranasal • Trivalent • Annual

35. Why a Yearly Influenza Vaccination • Influenza vaccine expires June 30 each year • Antibodies wane during the year • Surface antigens drift and shift

36. Inactivated Influenza Vaccine Efficacy • 70% - 90% effective among healthy persons <65 years of age • 30 - 40% effective among frail elderly persons • 50% - 60% effective in preventing hospitalization • 80% effective in preventing death

37. Influenza: High Risk for Complications • Birth through 59 months of age • Adults 50 years old and older • Chronic lung disease, asthma • Chronic heart disease • Metabolic diseases, e.g. diabetes • Chronic renal disease • High risk of aspiration • Immunosuppression • Pregnancy • Chronic aspirin therapy: 18 years old and younger

38. Influenza Antivirals

39. Influenza Antivirals • Use neuraminidase inhibitors • Oseltamavir: chemoprophylaxis and treatment • Zanamavir: treatment only • Avoid adamantanes due to resistance

40. Antivirals • M2 ion channel inhibitors • Amantadine • Rimantidine • Neuraminidase inhibitors • Tamiflu™ (Roche) • Relenza® (Glaxo-SmithKline)

41. Chemotherapy • Tamiflu (oseltamivir) – inhibits the neuraminidase and thus prevents the spread of the virus in the body • Tamiflu can therefore be used to reduce the length of illness and its transmission within a household • Resistance of H1N1 strain to oseltamivir has been reported at 25%

42. Oseltamivir • antiviral drug • neuraminidase inhibitor • treatment of influenza A and B (flu) • developed by Gilead Sciences (Donald Rumsfeld is a major stockholder of Gilead Sciences) • marketed by Hoffman-La Roche (Roche) • trade name Tamiflu®

43. Resistance Rate to Oseltamivir One study identified resistant isolates in 4 percentof treated children In a recent study of children treatedwith oseltamivir in Japan, 9 of 50 (18%) treated children harboredviruses with mutations in the neuraminidase gene that encodeddrug-resistant neuraminidase proteins If this frequent emergenceof resistant mutants is found to be a general occurrence inchildren, it is a serious concern, especially since childrenare an important source of the spread of influenza in the community

44. How to Minimize Problem of Drug Resistance for Influenza/ILI At this moment, any type of chemoprophylaxis of influenza with any antiviral (oseltamivir in this case) is strongly NOT recommended

45. Recommendations

46. Recommendations • Prevention is better than treatment

47. Recommendations –Healthy Habits • When Healthy: • Avoid close contact with those who are sick • Wash your hands often • Avoid touching your eyes, nose and mouth to decrease the spread of germs • When Ill: • Cover your mouth and nose with a tissue (or upper sleeve) when you sneeze or cough • Stay home from work or school when you are sick

48. Case Presentation ASUSH Chest Department

49. Personal History • A 52 years old female, born and living in Cairo, working as a professor of microbiology in national institute of research, married with 3 offspring the youngest has 18 years old • Pt had normal menses with no any contraceptive method • * No special habits of medical importance.

50. Complaint Complaining of shortness of breath of 5 days duration