1. INFLUENZA

2. INFLUENZA VIRUS

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

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

5. Influenza Antigenic Changes
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 5

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

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 11

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 15

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 18

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 19

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) 20

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. 21

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 22

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 23

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

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

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

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

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 32

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!) 33

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 34

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