influenza. influenza virus orthomyxoviruses m1 protein helical nucleocapsid (rna plus np protein) ha...
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INFLUENZA
INFLUENZA VIRUS
ORTHOMYXOVIRUSES
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
Influenza Virus
A/Fujian/411/2002 (H3N2)
Neuraminidase
Hemagglutinin
Type of nuclearmaterial
Virustype
Geographicorigin
Strainnumber
Year of isolation
Virus subtype
• 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
• Shift Major change, new subtypeExchange of gene
segmentMay result in pandemic
• Example:– H2N2 circulated from 1957-1967– H3N2 appeared in 1968 and completely
replaced H2N2
Influenza Antigenic Changes
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.
• 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.
• 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.
NORMAL TRACHEAL MUCOSA
3 DAYS POST-INFECTION 7 DAYS POST-INFECTION
• 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.
• 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
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.
SYMPTOMS
• FEVER
• HEADACHE
• MYALGIA
• COUGH
• RHINITIS
• OCULAR SYMPTOMS
• 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
• 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.
CLINICAL FINDINGS
• SEVERITY– VERY YOUNG– ELDERLY– IMMUNOCOMPROMISED– HEART OR LUNG
DISEASE
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
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)
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.
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
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
• 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
TYPE A
++++
yes
yes
yes
shift, drift
yes
sensitive
sensitive
2
severity of illness
animal reservoir
human pandemics
human epidemics
antigenic changes
segmented genome
amantadine, rimantidine
Zanamivir, Oseltamivir
surface glycoproteins
TYPE B
++
no
no
yes
drift
yes
no effect
sensitive
2
TYPE C
+
no
no
no (sporadic)
Drift?
yes
no effect
no effect
(1)
Diagnosis• Viral Isolation: PMK, MDCK
• Antigen Detection: IF
• Molecular Methods: Rt -PCR
• Serology: Hemagglutination
inhibition.
• Original antigenic sin.
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
OTHER TREATMENT
• REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6 months -18 years)
• BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY
EPIDEMIOLOGY
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.
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
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
• 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!)
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
The 3 Influenza Scenarios
• Seasonal flu
• Avian flu
• Pandemic flu