4. 8 SEGMENTS OF GENOME AND THEIR FUNCTION IN
INFLUENZA A
5. HAEMAGGLUTININ: GLYCOPROTEIN
SPIKES
Present in Trimer.
Mediates binding to sialic acid receptors on host cells.
Help in entry of the virus(receptor mediated endocytosis).
They cause haemaglutination in certain Fowl, Guinea pig and Human RBCs
Subtypes : H1-H18
Anti-haemagglutinin antibodies (Anti-H antibodies) provide protective immunity .
6. NEURAMINIDASE:
GLYCOPROTEIN ENZYME
SPIKES
Present as Tetramers.
Mushroom shaped
Aka RECEPTOR DESTROYING ENZYME
It has sialidase enzymatic activity(destroys sialic acid receptors on surface of host
cells)
Acts at end of replication cycle - release of virus from host cell.
Elution : Reversal of the haemagglutination. This is due to Neuraminidase.
7. TYPES OF INFLUENZA
4 Types
Influenza A – Mammals & birds
Influenza B – only Humans
Influenza C – Humans & Pigs(sometimes)
Influenza D
All known epidemics are caused by influenza A and B.
8. Subtypes of Influenza A : Based on Antigenicity of HA & NA , there are 18 HA (H1-H18)
subtypes and 11 NA (N1-N11) subtypes
Based on this we give the name as Eg : H1N1, H3N2, H5N8
Among these – H1, H2, H3, H5, H7, H9 – Can Infect Humans
N1, N2 – Infect Humans
Aquatics birds are susceptible to all the subtypes and are considered the primary
reservoir of the influenza A types.
9. ANTIGENIC VARIATION
ANTIGENIC DRIFT ANTIGENIC SHIFT
ANTIGENIC CHANGE GRADUAL SEQUENTIAL CHANGE IN
ANTIGENIC STRUCTURE OVER A PERIOD
OF TIME.
ABRUPT AND DRASTIC CHANGE
RESULTING IN NOVEL VIRUS
STRAIN UNRELATED
ANTIGENICALLY TO
PREDECESSOR STRAIN.
CHANGES DUE TO POINT MUTATION ON RNA SEGMENTS
(ESP HAEMAGGLUTININ).
GENETIC RECOMBINATION OF
HUMAN WITH ANIMAL OR
AVIAN STRAIN VIRUS.
(GENETIC REASSORTMENT)
RESULTS IN PERIODICS EPIDEMICS PANDEMICS AND EPIDEMICS
SEEN IN INFLUENZA A,B,C ONLY IN INFLUENZA A
PERIODICITY 2-3 YRS 10-12 YRS
14. Immunity
Immunity to influenza is subtype specific.
Antibodies against HA and NA are imp for immunity against influenza.
Resistance to initiation of infection is related to antibody against HA which neutralise
the viruses whereas decreased severity of disease and decreased ability to transmit
virus are related to antibody against the NA.
Antibodies against the ribonucleoprotein are type specific and useful in typing viral
isolates as in influenza A and B.
Protection correlates with both serum antibodies and secretory antibodies (IgA) in
nasal secretion.
15. A person with low titre of antibody may be infected but will experience a mild form
of illness.
All 4 types of influenza viruses are antigenically unrelated and therefore produce
no cross protection.
When a virus type undergo antigenic drift a person with prexisting antibodies to the
original strain may suffer only mild infection with the new strain
Antibodies appears in about 7 days after the attack and reach the maximum level
in about 2 weeks. After 8-12 months the antibody drop to pre infection level.
19. Complication
Most person who become ill with influenza virus infection recover without any
serious complication or sequele.
Complication of influenza most commonly occurs in HIGH RISK GROUP which
include :
Infants and young children,in particular <2 yrs of age
Pregnant women
Person with any age having chronic pulmonary disorder (Eg: Asthma and COPD).
Person with any age chronic chronic cardiac disease(congestive cardiac failure ).
Person with metabolic disorders
20. Person with CKD, Immonosupression, Malignancy.
Children receiving Chronic Aspirin Therapy.
Person aged >65 yrs of age.
21. Contd….
Most common complication of influenza is PNEUMONIA.
Pneumonia in influenza can be
1) Primary influenza viral pneumonia.
2) Secondary bacterial pneumonia.
3) Mixed viral and bacterial pneumonia.
Some influenza strain cause laryngotracheobronchitis,bronchiolitis or croup in
children.
Otitis media may be due to combination of influenza virus and bacteria.
22. Most common extra pulmonary manifestation is MYOSITIS which is seen more often
with influenza B and is characterised by severe muscle pain, elevated creatinine
phosphokinase levels and myoglobinuria that can lead to renal failure.
Myo/pericarditis is seen less frequently
Influenza associated encephalopathy /encephalitis
Post influenza acute demyelinating encephalomyelitis and Gullian Barre Syndrome
Use of aspirin for fever control and symptoms relieve in children with virus infection
was strongly discouraged because of development of REYE SYNDROME(acute
hepatic decompensation more commonly with influenza B virus)
23. Laboratory finding and diagnosis
Mild leucopenia is seen and if WBC count > 15000/microL suggest secondary
bacterial infection.
Virus detection:
a) Specimen : Nasopharyngeal specimen ideally within 48h of the onset of
symptoms.
b) Rapid influenza diagnostic test :Highly specific but sensitivity is 50-70%
c) NAAT: RT-PCR ,MULTIPLEX PCR
Mucosal antibody assay : with convalescent phase sample obtain 2 weeks after
infection.
24. Treatment
Influenza A infection could be treated with the M2 channel blockers AMANTADINE
AND RIMANTIDINE in the past, but currently circulating strains of influenza A are
resistant to these drugs.
Neuraminidase inhibitors(Inhibits release of virus from Host cells) have been the
mainstay of treatment of influenza A and B.
Use of Neuraminidase inhibitor should be considered in selected high risk group
discussed earlier.
The available neuraminidase are oral Oseltamivir, Nasal spray Zanamivir and
Intravenous Peramivir.
25. Oseltamivir is indicated for treatment of influenza
Recommended dose for Adults is 75mg BD for 5 days.
26. For infants < 1 yrs of age recommended oral doses is as
follows
a)14 days – 1month ::2 mg/kg BD for 5 days
b)>1 month -3 months::2.5 mg/kg BD for 5 days
c)>3 months-12 months ::3mg/kg BD for 5days
27. For older children recommended oral doses according to
weight band are as follows
a)15kgs or less---30mg BD for 5 days
b)15-23 kgs ---45 mg BD for 5 days
c)24-40 kgs---60mg BD for 5 days
d)>40 kgs---75 mg BD for 5 days
28. Zanamivir---zanamivir is indicated for the trearment of influenza in
adults and children > 5yrs. The recommended dose is two inhalation
BD for 5 days.
29. FDA approved for person > 12 yrs of age for prophylaxis and treatment
on uncomplicated influenza within 2 days of onset of illness.
Single dose formulation.
30. Infection control measure
Strict adherence to hand hygiene with soap and water or an alcohol based hand
sanitizer
Cover mouth and nose with tissue or handkerchief while coughing and sneezing.
Ill person wear face mask to reduce the risk of spreading the virus in the
community.
Whenever performing high risk aerosol generating procedure like bronchoscopy
use a particulate respirator mask (N95,FFP2 or equivalent),eye protection, gown,
gloves. Carry out procedure in an adequately ventilated room.
The duration of isolation for hospotalized patients with influenza symptoms should
be continued for 7 days after the onset of illness or 24 hours after the resolution of
fever whichever is longer.
32. These vaccine fall in 2 broad categories : Parenterally administered inactivated
influenza vaccine and intranasally administered live attenuated influenza vaccine.
Current inactivated influenza vaccine are designed with the common goal to induce
immunity to the haemagglutinin surface glycoprotein of the influenza virus. No effort
is made to standardize the neuraminidase content.
33. Trivalent IIVs contain three inactivated virus: type A(H1N1),type A (H3N2) and type B.
Quadrivalent influenza vaccine contain the same antigen as trivalent with addition of
another B strain virus.
The vaccine is available in both pediatrics(0.25 ml) and adult(0.5 ml) dose formulation.
One dose of IIVs may be administered annually for child 9 years of age and older .
Children 6 months to 8 yrs of age receiving influenza vaccine for the first time should
receive 2 doses administered atleast 28 days apart. Annual immunisation is
recommended
Vaccine becomes effective after 14 days of administration. Those infected shortly
before and shortly after the immunisation can still get the disease. Vaccinated individual
can also get infected with other strain of influenza virus from which vaccine does not
provide protection.
