Transcript document

INFLUENZA
INFLUENZA VIRUS
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
Influenza Virus
Type of nuclear
material
Neuraminidase
Hemagglutinin
A/Fujian/411/2002 (H3N2)
Virus
type
Geographic
origin
Strain
number
Year of
isolation
Virus
subtype
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
Influenza Antigenic Changes
• 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
Pathogenesis and Pathology
• Influenza virus can spread from person-toperson 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 mucousproducing 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
B
TYPE A TYPE TYPE
C
++
severity of illness
++++
+
no
animal reservoir
yes
no
no
human pandemics
yes
no
yes
human epidemics
yes
drift no (sporadic)
antigenic changes
shift, drift yes Drift?
segmented genome
no effect
yes
yes
amantadine, rimantidine sensitive sensitive
no effect
Zanamivir, Oseltamivir sensitive 2
no effect
surface glycoproteins
2
(1)
Diagnosis
•
•
•
•
Viral Isolation:
Antigen Detection:
Molecular Methods:
Serology:
PMK, MDCK
IF
Rt -PCR
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