INFLUENZA

1. INFLUENZA

2. INFLUENZA VIRUS

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

4. Influenza Virus Type of nuclear material Neuraminidase Hemagglutinin A/Fujian/411/2002 (H3N2) Virus type Geographic origin Strain number Year of isolation Virus subtype

5. Drift Minor change, same subtype Point mutations in gene May result in epidemic Example: In 1997, A/Wuhan/359/95 (H3N2) virus was dominant A/Sydney/5/97 (H3N2) appeared in late 1997 and became the dominant virus in 1998 Influenza Antigenic Changes

6. Shift Major change, new subtype Exchange of gene segment May result in pandemic Example: H2N2 circulated from 1957-1967 H3N2 appeared in 1968 and completely replaced H2N2 Influenza Antigenic Changes

8. Pathogenesis and Pathology Influenza virus can spread from person-to-person by the aerosol route. The major site of infection is the ciliated columnar epithelial cells. The first alteration is the disappearance of the elongated form of these cells which become round and swollen, the nucleus shrinks and fragments.

9. Vacuolization of the cytoplasm may occur and cilia are lost. Edema and inflammation follow with desquamation of the ciliated and mucous-producing epithelial cells down to a one-cell thick basal layer. Submucosal edema and hyperemia occur with an infiltration by neutrophils and mononuclear cells.

10. The extent of virus induced cellular destruction is the prime factor in determining the occurrence, diversity and duration of clinical illness. Reparative and destructive processes may be present simultaneously and complete resolution (repair) of the epithelial necrosis probably takes up to a month.

11. NORMAL TRACHEAL MUCOSA 3 DAYS POST-INFECTION 7 DAYS POST-INFECTION

12. Influenza virus induces pathological changes throughout the entire respiratory tract. Occasionally, it causes interstitial pneumonia sometimes with marked accumulation of lung hemorrhage and edema. Although it could be primary viral, most cases of pneumonia associated with influenza are caused by bacteria.

13. Recovery is associated with interferon production and the development of cellular immunity. Recovery precedes antibody production. Antibodies to HA, NA, NP and M proteins are produced. Viremia is rare

14. Clinical Features The incubation period ranges from 1 to 4 days with an average of 2 days but in children it may reach 7 days. The typical uncomplicated influenza syndrome is a febrile illness of sudden onset characterized by tracheobronchitis with the additional involvement of small airways. Most adults do not display the classic syndrome and it is uncommon in children and is not seen in infants.

15. SYMPTOMS FEVER HEADACHE MYALGIA COUGH RHINITIS OCULAR SYMPTOMS

16. Manifestations are related to: Common cold: Sneezing, nasal obstruction, nasal discharge. Upper respiratory illness: Nasal obstruction, discharge, sore throat. Pharyngitis: Sore throat and erythema Laryngitis: Hoarseness Tracheobronchitis: Cough

17. Children tend to have higher fever and febrile convulsions may take place. They also have a higher incidence of gastrointestinal manifestations. Infections in neonates can be life threatening. Otitis media, croup and myositis are more frequent in children.

18. CLINICAL FINDINGS SEVERITY VERY YOUNG ELDERLY IMMUNOCOMPROMISED HEART OR LUNG DISEASE

19. Persons at High Risk All persons 50 years of age or older Persons >6 months of age with chronic illness Residents of long-term care facilities Pregnant women (2nd and 3rd trimesters) Children 6 months to 18 years receiving chronic aspirin therapy Children 6-23 months of age

20. High risk due to Chronic Medical Conditions Pulmonary (e.g. COPD, asthma) Cardiovascular (e.g. CHF) Metabolic (e.g. diabetes) Renal (e.g. chronic renal failure) Hemoglobinopathies (e.g. sickle cell) Immunosuppression (e.g. HIV)

21. PULMONARY COMPLICATIONS CROUP (YOUNG CHILDREN) PRIMARY INFLUENZA VIRUS PNEUMONIA SECONDARY BACTERIAL INFECTION Streptococcus pneumoniae Staphlyococcus aureus Hemophilus influenzae Fatality is 10-12% but staphylococcal pneumonia may be fatal in 42% of cases.

22. NON-PULMONARY COMPLICATIONS myositis (rare, > in children, > with type B) cardiac complications recent studies report encephalopathy liver and CNS Reye’s syndrome peripheral nervous system Guillian-Barré syndrome

23. Reye’s syndrome liver - fatty deposits brain - edema vomiting, lethargy, coma Fatality ranges from 22 to 42%. risk factors youth certain viral infections (influenza, chicken pox) aspirin

24. In summary: Uncomplicated Influenza - Fever, Myalgia, headache Dry cough, nasal discharge and Ocular symptoms Pulmonary complications - Croup and Pneumonia Nonpulmonary complications - Myositis, Cardiac complications, Reye’s syndrome, and Guillain Barré syndrome

25. severity of illness animal reservoir human pandemics human epidemics antigenic changes segmented genome amantadine, rimantidine Zanamivir, Oseltamivir surface glycoproteins TYPE A ++++ yes yes yes shift, drift yes sensitive sensitive 2 TYPE B ++ no no yes drift yes no effect sensitive 2 TYPE C + no no no (sporadic) Drift? yes no effect no effect (1)

26. Diagnosis Viral Isolation: PMK, MDCK Antigen Detection: IF Molecular Methods: Rt -PCR Serology: Hemagglutination inhibition. Original antigenic sin.

27. TREATMENT - DRUGS RIMANTADINE (M2) type A only, needs to be given early AMANTADINE (M2) type A only, needs to be given early ZANAMIVIR (NA) types A and B, needs to be given early OSELTAMIVIR (NA) types A and B, needs to be given early

28. OTHER TREATMENT REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6 months -18 years) BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY

29. EPIDEMIOLOGY

30. Epidemiology Influenza is an Italian word reflecting an old belief that the illness was caused by the “influence” of atmospheric factors (stars). The viral etiology of the disease was first proven in 1933 in Ferrets by Sir Christopher Andrewes and coworkers.

31. The Story of Influenza: Historically Speaking Influenza is NOT a new illness Influenza can be traced as far back as 400 BC In Hippocrates’ Of the Epidemics, he describes a cough outbreak that occurred in 412 BC in modern-day Turkey at the turn of the autumn season

32. 412 BC Outbreak Actual disease that affected the camp is still under debate – but is theoretically influenza High communicable rate and autumn season onset are notable characteristics of influenza Death and funerals were a daily spectacle Miasma rising from bodies was fatal to the sick and the sick were fatal to the healthy Outbreaks were documented in the 18th and 19th century infecting about 70% of the population in some cities

33. Human influenza infection spreads by: Close contact (<6 feet) with a sick person who is coughing or sneezing, or Touching a surface contaminated by their respiratory secretions and getting the virus into mouth, nose or eyes. (WASH YOUR HANDS!)

34. Survival of Influenza in the Inanimate Environment and on Skin 24 – 48 hours on hard, non porous surfaces 8 – 12 hours on cloth, paper, and tissue 5 minutes on hand in water 22ºc → 4 days, 0ºc → 30 days at 60ºc for 30 mins inactivated by 70% alcohol and by Chlorine

35. The 3 Influenza Scenarios Seasonal flu Avian flu Pandemic flu