“This is scary and we don’t know…”

1. “This is scary and we don’t know…” “We don’t know the timing of the next pandemic, how severe it will be. We don’t know what drugs will work. We don’t have a vaccine. Yet we are telling everyone to prepare for a pandemic. It’s tricky…This is scary and we don’t know…that’s the message.” Dick Thompson World Health Organization December 2005

2. INFLUENZA - the name • Influenza is Italian for "influence", Latin: influentia. It used to be thought that the disease was caused by a bad influence from the heavens.

3. Flu sometimes is confused with the common cold. However, the flu is caused by influenza virus, and is a much more severe disease than the common cold, which is caused by a different type of virus. Influenza is a more severe viral infection of the respiratory tract that shows the additional symptoms to those of the common cold (rapidly rising fever, chills, and body and muscle aches).

5. INFLUENZA

6. Influenza is an acute systemic viral disease. • Has very serious complications. • Caused by influenza virus.

7. Classification • \Family is Orthomyxoviridae • Influenza family which is subdivided into 3 genera: A, B, and C, based on antigenic differences in the nucleoprotein (NP) and matrix (M) protein. 2. Influenza A viruses are further characterized by antigenic differences associated with the Haemagglutinin (HA) and Neuraminidase (N) glycoproteins; there are at least 15 subtypes of H and 9 subtypes of N proteins in influenza A virus. 3. All subtypes have been described in birds and some of them have been found in mammals.

8. Type A Type B • Humans • Swine • Birds • Horses • Seals • Humans Type C • Humans • Swine

9. Virus characteristics • Virion is 80-120 nm in diameter), enveloped, spherical to slightly pleomorphic in shape. • Underline the envelope is the Matrix ( M1 & M2) 2. Genome consists of 8 segments of ss RNA in A& B and 7 segments in C 3. The envelope contains 2 glycoproteins: H (hemagglutinin), and N (neuraminidase) 4. associated with the genome is nucleoprotein (NP)

11. HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex M1 protein ORTHOMYXOVIRUSES Type A, B, C : NP, M1 protein Sub-types: HA or NA protein

12. Influenza virus Hemagglutinin Neuraminidase A/Beijing/32/92 (H3N2) Virus type Geographic origin Strain number Year of Isolation Virus subtype

13. Influenza A is classified into subtypes based on HA & NA

14. DISEASE • Influenza A virus cause • worldwide epidemics (pandemic) • major outbreaks of influenza • occurs virtually every year. • Influenza B virus cause • major outbreaks of influenza

15. Nomenclature A/equine/Saskatoon/1/90(H3N8) Serotype of HA and N group year species Isolate number location • A/equine/Prague/1/56(H7N7) • A/fowl/Hong Kong/1/98(H5N1) • A/swine/Lincoln/1/86(H1N1)

16. Seasonal (human) Influenza ( H1N1) • Endemic • Strain varies slightly year to year • Avian Influenza (H5N1) • May be reservoir for completely new strains in humans • Can be Highly Pathogenic Avian Influenza (HPAI) • Pandemic Influenza (H1N1) • Global epidemic of new influenza A subtype in humans

17. ANTIGENIC CHANGES • Influenza viruses especially type A show changes in antigenicity of hemagglutinin (H) and neuraminidase (N) proteins. • Antigenic shifts: • major changes based on the reassortment of RNA segments. It occurs only with influenza A. • Other theories of antigenic shift includes: • Recirculation of existing subtypes • Gradual adaptation of animal viruses to human transmission • Antigenic drifts: • minor changes based on mutations in the RNA genome.

18. Animal viruses (aquatic birds, chicken, swine) are the source of RNA segments that encode antigenic shift variants. • Because influenza B virus is only a human virus, there is no animal source of new RNA segments. Influenza B virus shows only antigenic drift, but not shift.

19. Antigenic Variation • Due to:- • A. genome is segmented • Can infect wild range of different species. • It is RNA virus ( mutation more common). • Two forms

20. 1. Antigenic shift • Major change. • Occurs in influenza A only. • Result in a new subtype. • Associated with pandemic

21. Mechanism • Co-infection with 2 different subtypes usually avian and human occurs in pigs ( mixing vessel) .(same cell 2 subtypes) • Genetic reassortment occurs ( swapping of the genes) results in development of a new subtype

22. Reassortment

23. Pigs Serve As Mixing Vessels for reassortants • Pig cells contain receptors for both human and avian viruses. Aquatic birds and domestic Pigs Human Poultry (Human virus) (Avian virus) Human (reassortant virus)

24. A/ PHILIPPINES / 82 (H3N2) • A group antigen of influenza A • Philippines / 82 location and year the virus isolated • H3N2 Hemagglutinin and Neuraminidase types • H1N1 and H3N2 strains of influenza A are the most common types at this time and are the strains included in the current vaccine.

25. Past Antigenic Shifts 1918H1N1 “Spanish Influenza” 20-40 million deaths 1957H2N2 “Asian Flu” 1-2 million deaths 1968H3N2 “Hong Kong Flu” 700,000 deaths 1977H1N1 Re-emergence No pandemic • At least 15 HA subtypes and 9 NA subtypes occur in nature. Up until 1997, only viruses of H1, H2, and H3 are known to infect and cause disease in humans.

26. 2. Antigenic drift • Minor change. • Occurs in influenza A & B • Occurs between epidemics. • Results in seasonal localized outbreaks.

27. Mechanism • Due to cumulative point mutations in the HA gene

29. Transmission • Airborne – droplets – esp. crowded populations in enclosed spaces • Direct contact – virus may persist on object for hours to days – esp. in cool, dry areas • Incubation – 1 – 3 days • Communicable – 1-2 days before onset of symptoms and 4-5 days after onset • Possibly up to 21 days in < 12 y.o. or adults w/ avian

30. Influenza spread Courtesy of Centers for Disease Control and Prevention

31. Clinical Features • Incubation period 24 – 48 hours • Sudden onset of fever with chills , myalgias, headache, dry cough, photophobia, sore throat • Diarrhoea and vomiting may occur • Resolve spontaneously in 4 – 7 days.although cough and malaise can persist for >2 weeks. Influenza B is similar to A, but influenza C is usually subclinical or milder in nature.

32. Complications • Tend to occur in the • young, • elderly, • pregnants • persons with chronic cardio-pulmonary diseases. • Persons with chronic diseases :DM,renal,liver • Immunocompromized patients

33. COMPLICATIONS • Tracheobronchitis and bronchiolitis • Croup • Primary viral pneumonia • Secondary bacterial pneumonia • usually occurs late in the course of disease, after a period of improvement has been observed for the acute disease. S. aureus is most commonly involved although S. pneumoniae and H. influenzae may be found. • Myositis and myoglobinuria

34. Reye's syndrome • Reye's syndrome is characterized by encephalopathy and fatty liver degeneration. It occurs in children with viral infection and are taken aspirin to reduce fever. The disease had been associated with several viruses; such as influenza A and B, Coxsackie B5, echovirus, HSV, VZV, CMV and adenovirus. • Myocarditis and pericaditis

35. LABORATORY DIAGNOSIS • Virus Isolation • Specimens :Throat swabs, Nasopharyngeal aspirate (NPA) and nasal washings may be used for virus isolation.. Influenza viruses isolated from embryonated eggs or tissue culture can be identified by serological or molecular methods. • Rapid Diagnosis by Immunoflurescence(Antigen detetection) • cells from pathological specimens may be examined for the presence of influenza A and B antigens by indirect immunofluorescence. • Nucleic acid detection using PCR ( same specimen as above)

36. Serology • Demonstration of a rise in serum antibody to the infecting virus

37. TREATMENT • Amantidine • The only effective against influenza A. • Act at the level of virus uncoating inhibit M2 protein. • Both therapeutic and prophylactic effects. • Significantly reduces the duration of fever (51 hours as opposed to 74 hours) and illness. • 70% protection against influenza A when given prophylactically. • Rimantadine is an amantadine derivative but not as effective as amantadine and less toxic.

38. Neuraminidase inhibitors - zanamivir (given by inhalation) - oseltamivir (orally) Used for influenza A and B including pandemic H1N1 Used for treatment and prophylaxis • To be maximally effective the drugs must be administered very early in the disease.

39. Amantadine Rimantadine Zanamivir Oseltamivir Type of Influenza virus infection indicated for use Influenza A Influenza A Influenza A Influenza B Influenza A Influenza B Administration oral oral oral inhalation oral Ages approved for treatment of flu 1 year 14 year 7 years 18 years Ages approved for prevention of flu 1 year 1 year not approved not approved Anti-viral drugs: General background

40. PREVENTION • Vaccine • Protection lasts only 6 months • Yearly boosters are recommended • Should be given to people • Older than 65 years • With chronic respiratory diseases • With chronic cardiovascular diseases. • Immunity to Influenza • Antibody against hemagglutinin (H) is the most important component in the protection against influenza viruses.

41. Influenza Vaccines • Though existing vaccines are continually being rendered obsolete as viruses undergo antigenic drift and shift. • Yet controlled trials of influenza vaccines indicate that a moderate degree of protection (50-80%) is attainable.

42. 1) Inactivated influenza vaccines • Is a trivalent vaccine containing (H1N1 ,H3N2 and B ) • Vaccines are either whole virus (WV) vaccine which contains intact, inactivated virus • or subvirion (SV) vaccine: • contain purified HA and NA glycoproteins. .

43. 2) Live influenza vaccines: • The only feasible strategy to develop a live-virus vaccine is to devise a way to transfer definedattenuating genes from an attenuated master donor virus to each new epidemic or pandemic isolate. • A cold-adapted influenza virus (able to grow at 25C but not at 37C) introduced intranasally should replicate in the nasopharynx but not in the lower respiratory tract, its multiplication stimulate the local production of IgA. • ( Flumist)

44. Good luck

45. AVIAN INFLUENZA • Avian influenza A viruses usually do not infect humans • Rare cases of human infection with avian influenza viruses have been reported since 1997 with avian influenza A (H5N1) viruses • All strains of the infecting virus were totally avian in origin and there was no evidence of reassortment. • Infection in humans are thought to have resulted from direct contact with infected poultry or contaminated surfaces. • To date, human infections with avian influenza A viruses have not resulted in sustained human-to-human transmission.

47. PICORNAVIRUSES

48. PICORNAVIRUSES • Small (20 – 30 nm) non–enveloped viruses, with icosahedral nucleocapsid and ssRNA genome with positive polarity. • Includes two groups: • Enteroviruses • Enteroviruses include poliovirus, coxsackieviruses, echovirus and hepatitis A virus. • replicate optimally at 37 ºC • Enteroviruses are stable under acid conditions (pH 3 – 5) • Rhinoviruses • Rhinoviruses grow better at 33 ºC in accordance with the lower temperature of the nose. • Rhinoviruses are acid – labile.

49. RHINOVIRUSES

50. RHINOVIRUSES • Common cold accounts for 1/3 to 1/2 of all acute respiratory infections in humans. • Rhinoviruses are responsible for 50% of common colds, coronaviruses for 10%, adenoviruses, enteroviruses, RSV, influenza, parainfluenza can also cause common cold symptoms indistinguishable form those caused by rhinoviruses and coronaviruses. • Common cold is a self-limited illness. • More than 100 serologic types of rhinoviruses (No vaccine)