This ppt is about influenza virus, its epidemiology, replicative stages and management.

1. Dr Asif Hussain
JR-2
JNMCH, AMU

2.  An acute respiratory illness caused by influenza viruses.
 Affects the upper and/or lower respiratory tract.
 Nearly every year outbreaks of illness occurs of variable
extent and disease severity.
 Result in significant morbidity in general population and
increased in mortality rates among high-risk patients.

3.  Shortness of breath
 Pain or pressure in the
chest or abdomen
 Dizziness
 Confusion
 Severe or persistent
vomiting
 Flu-like symptoms
improve but then return
with fever and worse
cough

4.  Dyspnoea
 Bluish discoloration of skin
 Not drinking enough fluids
 Severe or persistent vomiting
 Not waking up or not interacting
 Irritable
 Flu-like symptoms

5.  Birth to 4 years old
 Pregnant women
 >65 years old
 Long-term aspirin therapy
 Disorders of the pulmonary or cardiovascular system.
 Metabolic diseases

6.  Outbreaks recorded virtually every year, their extent
and severity varies.
 Localized outbreaks take place at variable intervals,
usually every 1–3 years.
 The most recent pandemic emerged in March of 2009.
 Caused by an influenza A/H1N1 virus that rapidly
spread worldwide over several months.

7.  RNA viruses of orthomyxoviridae family ,influenza A, B, and
C viruses are clinically important.
 A, B, or C is based on antigenic characteristics of the
nucleoprotein (NP) and matrix (M) protein antigens.
 Influenza A viruses are further subdivided on the basis of
the surface hemagglutinin (H) and neuraminidase (N)
antigens .
 individual strains are designated according to the site of
origin, isolate number, year of isolation, and subtype—for
example, influenza A/California/07/2009 (H1N1).

8.  Influenza A has 16 distinct H subtypes and 9 distinct N
subtypes.
 H1, H2, H3, N1, and N2 have been associated with
epidemics of disease in humans.
 Influenza B and C viruses are similarly designated, H
and N antigens from these viruses do not receive
subtype designations.
 Intratypic variations in influenza B :less extensive ,
 In Influenza C virus: Absent

9.  The hemagglutinin is the site by which the virus binds
to sialic acid cell receptors, whereas the neuraminidase
degrades the receptor and plays a role in the release of
the virus from infected cells after replication has taken
place.

11.  Samples
 Nasal swab/wash
 Tracheal aspirate
 Laboratory findings
1. Leukopenia and/or lympopenia
2. Elevated Serum lactate dehydrogenase (LDH)
Management

12.  Investigations:
 Rapid antigen detection
 Immunofluorescence
 Nucleic acid test : rRT-PCR
 Viral culture
 Antibody testing

13.  Supportive
 Isolation
 Oxygen therapy
 Intravenous hydration
 Symptomatic relief
 Critical care needs: ventilatator, hemodynamic support.
 Antiviral therapy
 Adjunct therapy:Prophylactic antibiotics

14.  Benefits of antiviral therapy
 Shortening the duration of symptoms
 Decreases the risk of complicated disease
 Decreases viral shedding
 Timing
 Best if initiated with in <48 hrs of initiation
 May still help after 48 hr if the symptoms are severe or
pregnant patient

15.  Secondary bacterial infection
 Retrospective pathological review suggested secondary
bacterial infection as the major cause of death in
pandemic H1N1 in 1918
 Occurs several days after onset
 Staphylocoocci aureus including MRSA
 Nacrotizing pneumonia
 Pneumatocele
 Gram negative bacteria

16. Inhibitors of viral penetration and
uncoating
Amantadine
Rimantadine
Neuraminidase inhibitors
Oseltamavir
Zanamavir
Peramivir

17.  Amantadine and its -methyl derivative rimantadine are
uniquely configured tricyclic amines.

18.  They inhibit an early step in viral replication, viral
uncoating.
 Have an effect on a late step in viral assembly.
 Site of action :M2 protein, an integral membrane
protein that functions as an ion channel.
 Drug inhibit the acid-mediated dissociation of the
ribonucleoprotein complex in replication.

19. Side effects include :
 nervousness,
 light-headedness,
 difficulty concentrating,
 insomnia, and
 loss of appetite
 Nausea & vominting
 Ankle edema

20.  Seasonal prophylaxis: amantadine or rimantadine (200
mg/day) is ~70-90% protective against influenza A illness.
 Pandemic influenza, in preventing nosocomial influenza
and outbreaks.
 Treatment : Influenza A , modest effect
(100mg bd x 5 days)

21.  First orally active neuraminidase inhibitor
 Mechanism of action
 Oseltamivir is a prodrug
 Competitive inhibitor of
sialic acid, found on the surface proteins of normal host
cells
 Blocking the activity of the viral neuraminidase enzyme,
oseltamivir prevents new viral particles from being
released by infected cells

23. Dosing
 Given to >1 yr of age
 TREATMENT :75 mg twice daily for 5 days
 PROPHYLACTIC : 75 mg once daily for 14 days shown to
be safe and effective for up to six weeks

24. Side effects
 Common ADRs:-Nausea, vomiting, diarrhea,
abdominal pain, and headache.
 Rare ADRs include: hepatitis and elevated liver
enzymes, rash, allergic reactions including
anaphylaxis, and Stevens-Johnson syndrome
 Postmarketing surveillance: toxic epidermal
necrolysis, cardiac arrhythmia, seizure, confusion,
aggravation of diabetes

25.  Zanamivir is a sialic acid analog tha inhibits the
neuraminidases of influenza A and B viruses.
 Pharmacokinetic data
 Bioavailability- 2% (oral)
 Protein binding- <10%
 Metabolism- Negligible
 Half life- 2.5–5.1 hours
 Excretion- Renal
 Routes- Inhalation

26.  Mechanism of action
 Zanamivir works by binding to the active site of the
neuraminidase protein, rendering the influenza virus
unable to escape its host cell and infect others.
 It is also an inhibitor of influenza virus replication in
vitro and in vivo

27.  Dosing
 Two inhalation (10 mg per puff) twice a day for 5 days
 After inhalation, zanamivir is concentrated in the lungs
and oropharynx,
 15% of the dose is absorbed and excreted in urine

29. Side effects
 Headache
 Bronchospasm and cough (contraindicated in asmatics)
 Zanamivir has not been known to cause toxic effects,
does not spread around through the body's systemic
circulation and
 No signs of viral resistance from any flu

30. Age group (in years)
Antiviral drug Children≤ 12 13-64 ≥65
Oseltamivir
Treatment (A&B) <15 kg: 30 mg bd; >15–23 kg: 45
mg bd; >23–40 kg: 60 mg bd
75mg po bd 75mg po bd
Prophylaxis(A&B) <15 kg: 30 mg od; >15–23 kg: 45
mg od; >23–40 kg: 60 mg od
75mg od 75mg od
Zanamivir
Treatment (A&B) 10mg bd inhalation 10mg bd 10mg bd
Prophylaxis(A&B) 10mg od 10mg od 10mg od
Amantadine
Treatment (A) Age 1–9, 5 mg/kg in 2 divided
doses, up to 150 mg/d
Age 10, 100 mg
PO bd
≤ 100 mg/d
Prophylaxis, (A) Age 1–9, 5 mg/kg in 2 divided
doses, up to 150 mg/d
Age 10, 100 mg
PO bd
≤ 100 mg/d
Rimantadine
Treatment, (A) Not approved 100 mg PO bd 100–200 mg/d
Prophylaxis, (A) Age 1–9, 5 mg/kg in 2 divided
doses, up to 150 mg/d
Age 10, 100 mg
PO bd
100–200 mg/d

32.  Avoid close contact
With sick people. Keep safe distance
 Stay home when you are sick
If possible, stay home from work, school and office
 Cover your mouth and nose
Cover mouth and nose with tissue when coughing or
sneezing
 Clean your hands
Frequent hand washing will protect you from germs
 Avoid touching your eyes, nose or mouth

33.  Drink plenty of fluids and eat nutritious food
 Get plenty of sleep to be physically active.
 Manage your stress.
 Get treatment and/or prevention of the infection with
antiviral drugs.

34. Hand washing technique

35. Facemasks (disposable, single use masks) for
persons who enter crowded settings
Respirators (N95 or higher filtering facepiece
respirator) for persons who have unavoidable close
contact with infectious person
No clear scientific evidence regarding the effectiveness of facemasks
and respirators in protecting against influenza
When contact is unavoidable

36.  Medical institutions
 To maintain good infection control
 Schools
 To perform preventive measures such as morning
inspection, temperature measurement, school
suspension for the sick, outbreak notification

37.  The influenza vaccine, also known as flu shot, is an
annual vaccination using a vaccine specific for a given
year to protect against the highly variable influenza virus
 Two types of influenza vaccines are available:
 TIV :of trivalent (three strains; usually A/H1N1, A/H3N2,
and B) inactivated (killed) vaccine)
 LAIV: (nasal spray )of live attenuated influenza vaccine

38.  Mechanism of action
 TIV works by putting into the bloodstream those parts
of three strains of flu virus that the body uses to create
antibodies
 LAIV works by inoculating the body with those same
three strains, but in a modified form that cannot cause
illness.
 Prepration
 Pandemrix by GlaxoSmithKline (GSK)
 Focetria by Novartis