1. INFLUENZA
TUCOM
Internal Medicine
4th year
Dr. Hasan.I.Sultan

2. UPPER RESPIRATORY TRACT INFECTIONS
RESPIRATORY INFECTIONS CAUSED BY VIRUSES
Clinical syndrome
Usual cause
Epidemic influenza
Influenza A and B
Sore throat
Adenoviruses
Common cold (coryza)
Rhinoviruses
Croup
Parainfluenza 1, 2, 3
Bronchitis
Rhinoviruses, adenoviruses
Bronchiolitis
Respiratory syncytial virus
Pneumonia
Influenza A and B, chickenpox

3. Influenza What do you know about Influenza viruses?
Influenza is an acute respiratory illness caused by infection with influenza viruses.
The illness affects the upper and/or lower respiratory tract and is often accompanied by systemic signs and symptoms such as fever, headache, myalgia, and weakness. Outbreaks of illness occur nearly every winter.
Such outbreaks result in significant morbidity and mortality in the general population.

4. Influenza viruses are RNA viruses in the family Orthomyxoviridae that can affect birds and mammals including humans. They have surface projections are molecules of hemagglutinin and neuraminidase. There are three types of influenza: Influenza A; Responsible for regular outbreaks and pandemic. Influenza A viruses also infect domestic animals (pigs, horses, chickens, ducks) and some wild birds. Influenza B; Often causes sporadic outbreaks of illness, it is human pathogen only. Influenza C; Seldom causes disease symptoms, human pathogen only.

5. Genes of Influenza A
Sheathed in a lipid bilayer (derived from the plasma membrane of its host cell). Studded in the lipid bilayer are two integral membrane proteins: hemagglutinin ("H") and neuraminidase ("N"). Within the lipid bilayer are matrix protein and 8 pieces of RNA.
The HA gene. It encodes the hemagglutinin. 3 distinct hemagglutinins (H1, H2, and H3) are found in human infections; 13 others have been found in animal flu viruses.
 The NA gene. It encodes the neuraminidase. 2 different neuraminidases (N1 and N2) have been found in human viruses; 7 others in other animals.

7. Antigenic change in influenza viruses can occur:
gradually (antigenic drift), which is the minor mutation of the surface glycoproteins, namely hemagglutinin (H) and neuraminidase (N), that leads to seasonal epidemics that occur in winter every year.
or suddenly (antigenic shift ), which is a major change to the virus structure to create an absolutely new subtype of influenza virus, that associated with pandemics and enables a flu strain to jump from one animal species to another.
What events will lead to an influenza pandemic?
Antigenic evolution of an influenza virus to which humans have little or no immunity, so it easy spread among susceptible humans.
The hemagglutinin of the 1918 flu virus was H1, its neuraminidase was N1, so it is designated as an H1N1 "subtype".
The data suggest that flu pandemics occur when the virus acquires a new hemagglutinin and/or neuraminidase.

8. Here are some strains of influenza A
Date
Strain
Subtype
Notes
1918
H1N1
pandemic of ”Spanish flu”
1957
A/Singapore/57
H2N2
pandemic of "Asian" flu
1962
A/Japan/62
epidemic
1964
A/Taiwan/64
1968
A/Aichi/68
H3N2
pandemic of "Hong Kong" flu
1976
A/New Jersey/76
swine flu in recruits
1977
A/USSR/77
"Russian" flu
2009
A/California/09
pandemic of ”Swine flu”

9. 1918 flu pandemic. It occur at the end of World War I (10 million death from war). It infected 500 million people across the world, and killed 20 to 40 million of them (3 to 5 percent of the world's population) making it one of the deadliest natural disasters in human history.

10. The Bird Flu;
In October 2003, an epidemic of influenza in chickens began sweeping through several countries (Vietnam, Thailand, Japan, China, South Korea, Cambodia). The virus is H5N1. The H5 molecule is common among bird influenza viruses but has not been seen on flu viruses that cause human epidemics. However, sporadic human cases of H5N1 (with an alarmingly-high fatality rate) have been occurring ever since.

11. The Swine Flu of 2009; A new H1N1 flu began infecting humans in North America in April 2009 and has now spread throughout much of the world. The amino acid sequence of its H1 molecules closely resemble those found in the 1918 flu virus, so that enabled the virus to jump so successfully from pigs to humans.

12. Clinical features
Epidemics of influenza A occur almost exclusively during the winter months.
An abrupt illness affects the upper (cough, sore throat, substernal discomfort) and/or lower respiratory tract (dyspnea, wheezes, rhonchi, scattered rales or signs of consolidation) accompanied by systemic signs and symptoms such as headache, fever (temperatures of 38°–41°C), chills, diaphoresis, myalgia, arthralgias, weakness, and malaise.
Most patients have largely recovered in 1 week.

13. When might microbiological investigations be appropriate?
Diagnosis usually made on clinical ground, but microbiological investigations may be appropriate for immunocompromized patient, unusual clinical presentation or serious systemic illness. This done by; antigenic detection with immunofluorescence and PCR, these methods are preferable to culture and serology.
What are the complications of influenza?
Tracheitis, bronchitis, bronchiolitis and bronchopneumonia.Secondary bacterial invasion by Strep. pneumoniae, H. influenzae and Staph. aureus may occur.
Toxic cardiomyopathy may cause sudden death (rare).
Encephalitis, demyelinating encephalopathy and peripheral neuropathy are also rare complications.

14. What preventative measures are available for influenza?
Flu Vaccines; inactivated component of influenza virus, which reviewed each year by WHO to ensure a closed match to influenza strains. The protection is % when viral strain is matched.
Annual Immunization is recommended for;
Patient over 65 year
Chronic respiratory diseases
Chronic heart diseases
Chronic renal diseases
Chronic liver diseases
Immunosuppression

15. What antiviral treatment of influenza?
Amantadine and Rimantadine;
These drugs inhibit the matrix protein needed to get viral RNA into the cytosol. They work against A strains only, and resistance to the drugs evolves quickly.
Zanamivir (Relenza®) and Oseltamivir (Tamiflu®);
These drugs block the neuraminidase and thus inhibit the release and spread of fresh virions. Spraying zanamivir into the nose or inhaling it shortens the duration of disease symptoms by one to three days. Unfortunately, by the flu season, all H1N1 strains circulating in the U.S. had become resistant to Tamiflu.

16. Thanks