Full information on H1N1

1. H1N1 Influenza
(Swine Flu)
CHAIRPERSON: DR. P.V. VENKATARAMANAPPA
PRESENTER: DR. M. RAMESH BABU
M.V.J. MEDICAL COLLEGE

2. INTRODUCTION
 Swine influenza is a highly contagious respiratory
disease in pigs caused by one of several swine
influenza A viruses.
 In addition, influenza C viruses may also cause illness
in swine.
 Transmission of swine influenza viruses to humans is
uncommon.
 The swine influenza virus can be transmitted to
humans via contact with infected pigs or
environments contaminated with swine influenza
viruses.
 Once a human becomes infected, then spreads the
virus to other humans, in the same way as seasonal
influenza spread

3. HISTORY
 The outbreaks of swine flu in humans - 1918 Spanish
influenza pandemic, which infected 1/3rd
of the world’s
population (an estimated 500 million people) and
caused approximately 50 million deaths.
 The cause of human influenza and its links to avian and
swine influenza was not understood.
 In1930s related influenza viruses (now known as H1N1
viruses) were isolated from pigs and then humans.
 In humans, the severity of swine influenza can vary from
mild to severe.
 A 1976 outbreak of swine influenza in Fort Dix, New
Jersey, involved > 200 cases, some of them severe, and
one death.
 The first discovered case involved a soldier at Fort Dix
who complained of feeling weak and tired. He died the
next day.

5. Epidemic of ‘Swine Flu’ in India
 The 2009 flu pandemic in India was the outbreak of
swineflu.
 This was the first epidemic attributed to this infection in
India.
 Soon after the outbreak of H1N1 virus in the United States
and Mexico in March 2009, the Government of India
started screening people coming from the affected
countries for swine flu symptoms at airports.
 The first case of the swine flu in India was found at
Hyderabad airport on 13 May 2009, when a man
travelling from US to India was found H1N1 positive.
 In 2009 swine flu outbreak in India had affected mostly its
main cities.

6. Current scenario 2015

8. INFUENZA
 Orthomyxoviruses
 -pleomorphic
 Irrerugar spherical
 80-120 nm in diameter

9. ORTHOMYXOVIRUS

10. Influenza Subtypes
Types A & B
3 IMPs
HA
NA
M2
8 Segments of RNA
Responsible for epidemics &
pandemics
Type C
1 IMP
HEF
Serves functions of both HA
and NA
7 Segments of RNA
Causes only mild infections
Influenza strains are subtyped A, B, or C based on the
relatedness of the matrix (M1) and nucleoprotein (NP) antigens
All 3 subtypes can infect human, subtype A can also infect
other mammals and birds
Within each subtype, there are many variant strains

11.  There are 16 Hemagglutinin ( H ) antigens 1 to 16
Neuraminidase ( N ) antigens 1 to 9
All 16 (H) subtypes of influenza A viruses readily infect the
birds
viruses having any of the H1, H2, H3 antigens and any of the
N1 or N2 antigens only infect humans
H1N1, H2N2, & H3N2 types of influenza A associated with
most of the wide spread epidemics and pandemics.
Humans can infect influenza viruses that routinely
circulating in animals such as avian influenza virus A
H5N1 & H9N2 and swine flu viruses subtypes A H1N1 &
H3N2.

13. Genetic Reassortment (HA & NA)
Antigenic Drift
 Minor changes in the antigenic character
 Mutation rate highest for type A, lowest for type C
 Most meaningful mutations occur in HA1 protein
 When 2 virions infect a cell, there are 256 possible
combinations of RNA for offspring.

14. Antigenic Shift
 Phylogenic evolution that accounts for emergence of
new strains of virus
 Immunologically distinct, novel H/N combinations
 Genetic reassortment between circulating human and
animal strains is responsible for shifts
 Segmented genome facilitates reassortment
 Only been observed in type A, since it infects many
species

16. TRANSMISSION
 AEROSOL:100,000 TO 1,000,000 virions per droplet.
 Influenza is spread from person-to-person by contact with
respiratory secretions from an infected person.
 When an infected person coughs or sneezes, the viruses
are carried in large droplets which settle on the surfaces
of the upper respiratory tracts of persons who are nearby
(i.e. within 3 feet of the infected person).
 The viruses can also spread by direct or indirect contact
with respiratory secretions –
 Touching objects contaminated with particles from an
infected person’s nose and throat
 18-72 hrs. INCUBATION

17.  Infected Person Can Infect Others:
 Beginning 1 Day Before Symptoms Develop
 Up to 7 Days or More After Becoming Sick
 Younger Children – May Be Contagious for Longer
Periods

18. Routes of Exposure to Spread the Infection
 Primary Exposure Route – Person to Person
 Inhalation of Airborne Droplets from Infected Person
Coughing or Sneezing
 Secondary Route of Exposure -Viruses on Surfaces
 Can Live on Surfaces for 2 Hours or More
 Person Touching Contaminated Tables, Doorknobs, Desks
- Then Touching Face, Eyes, Nose, or Mouth.

19. Influenza viruses enter
cells by receptor-
mediated endocytosis,
forming a virus-
containing endosome.
The viral hemagglutinin
mediates fusion of the
endosomal membrane
with the virus envelope,
and viral nucleocapsids
are subsequently
released into the
cytoplasm.
Pathogenesis and Immunity

20.  Viral infection involves the ciliated columnar epithelial
cells, but it may also involve other respiratory tract cells,
including alveolar cells, mucous gland cells, and
macrophages.
 In infected cells, virus replicates within 4–6 h, after which
infectious virus is released to infect adjacent or nearby
cells.
 The cells eventually become necrotic and desquamate;
previously columnar epithelium is replaced by flattened
and metaplastic epithelial cells.
 The host response to influenza infections involves a
complex interplay of humoral antibody, local antibody,
cell-mediated immunity, interferon, and other host
defenses.
 Virus shedding generally stops within 2–5 days after
symptoms first appear

21. VIRUS
CLEARANCE OF VIRUS
IMMUNITY

22. CYTOKINE STORM and the INFLUENZA
PANDEMIC
 A cytokine storm is the systemic expression of a healthy
and vigorous immune system resulting in the release of
more than 150 inflammatory mediators (cytokines,
oxygen free radicals, and coagulation factors).
 Both pro-inflammatory cytokines (such as Tumor
Necrosis Factor-alpha, InterLeukin-1, and InterLeukin-6)
and anti-inflammatory cytokines (such as interleukin 10,
and interleukin 1 receptor antagonist) are elevated in
the serum, and the fierce and often lethal interplay of
these cytokines is referred to as a "Cytokine Storm".
 The primary contributors to the cytokine storm are TNF-a
(Tumor Necrosis Factor-alpha) and IL-6 (Interleukin-6)..

23.  The cytokine storm is an inappropriate (exaggerated)
immune response that is caused by rapidly proliferating and
highly activated T-cells or natural killer (NK) cells. These cells
are themselves activated by infected macrophages. The
cytokine storm must be treated and suppressed or lethality
can result.
 Acute respiratory viral infection ( influenza virus) results in a
cytokine storm effecting the lungs, and subsequent
damage to alveoli and lung tissue results in the lethality seen
in more severe flu viral infections, especially those fatalities
among young healthy adults.
 In the absence of prompt medical intervention to stop the
"cytokine storm", the lung will suffer permanent damage.
Many of these patients will develop acute respiratory distress
syndrome (ARDS), i.e. will present with pulmonary edema
that is not caused by volume overload, or a depressed left
ventricular function. Deaths will usually result from
multisystem organ failure, and not from lung failure

24. Proposed Mechanism of the Cytokine Storm
Evoked by Influenza virus:

25. SYMPTOMS OF THE CYTOKINE STORM:
 The end stage, or final result, of cytokine storm (SIRS) or sepsis is
multiple organ dysfunction syndrome (MODS). The end-stage
symptoms of the bird flu, or other infection precipitating the
cytokine storm may include:
 hypotension
 tachycardia
 dyspnea
 fever (temperature of >38°C or >100.4°F)
 Ischemia, or insufficient tissue perfusion (especially involving the
major organs)
 uncontrollable hemorrhage
 and multisystem organ failure (caused primarily by hypoxia, tissue
acidosis, and severe metabolism dysregulation

26. Persons at risk for influenza (H1N1)
 Infants and young children, in particular <2 years
 Persons aged 65 years and older
 Pregnant women
 Persons of any age with chronic pulmonary disease (e.g.
asthma, COPD)
 Persons of any age with chronic cardiac disease (e.g.
congestive cardiac failure)
 Persons with metabolic disorders (e.g. diabetes)
 Persons with chronic renal disease, chronic hepatic
disease, certain neurological conditions (including
neuromuscular, neurocognitive and seizure disorders.
 Hemoglobinopathies
 Immunosuppression
 Children receiving chronic aspirin therapy

29.  The most common clinical findings of the 2009 H1N1 influenza
A pandemic were:
 fever, cough, sore throat, malaise, and headache; vomiting
and diarrhea were also common, both of which are unusual
features of seasonal influenza .
 Other frequent findings included chills, myalgias, and
arthralgias .
 Among 268 patients in the United States requiring
hospitalization for pandemic H1N1 influenza A infection,
clinical findings included
 fever (93 %) cough (83 %),
 shortness of breath (54 %), fatigue or weakness (40 %),
 chills (37 %), myalgias (36 %),
 rhinorrhea (36 %), sore throat (31%),
 headache (31 %), vomiting (29 %),
 wheezing (24 %), and diarrhea (24 %).
 United States Centers for Disease Control and Prevention. 2009 H1N1 early outbreak and disease
characteristics http://www.cdc.gov/h1n1flu/surveillanceqa.htm (Accessed on October 13, 2011).

30. CASE DEFINITIONS
The following case definitions have been provided by the
United States Centers for Disease Control and Prevention
(CDC) :
Influenza-like illness (ILI) is defined as fever (temperature
of 100ºF [37.8ºC] or greater) with cough or sore throat in
the absence of a known cause other than influenza.
Confirmed case defined as an individual with an ILI with
laboratory-confirmed H1N1 influenza A virus detection by
real-time reverse transcriptase polymerase chain reaction
(rRT-PCR) or culture.

31. DEFINITIONS OF ILLNESS SEVERITY
Mild or uncomplicated illness : is characterized by
fever,
cough,
sore throat,
rhinorrhea,
muscle pain,
headache,
chills,
malaise, and sometimes diarrhoea and vomiting, but
no shortness of breath and little change in chronic
health conditions.

32.  Progressive illness : is characterized by typical
symptoms plus signs or symptoms such as
 chest pain,
 poor oxygenation (eg, tachypnea, hypoxia),
 cardiopulmonary insufficiency (eg, hypotension),
 central nervous system (CNS) impairment (eg, confusion,
altered mental status),
 severe dehydration, or exacerbations of chronic
conditions (eg, asthma, chronic obstructive pulmonary
disease,
 chronic renal failure, diabetes, or other cardiovascular
conditions).

33.  Severe or complicated illness: is characterized
by signs of
 lower respiratory tract disease (eg, hypoxia requiring
supplemental oxygen, abnormal chest radiograph,
mechanical ventilation),
 CNS findings (encephalitis, encephalopathy),
 Complications of hypotension (shock, organ failure),
 Myocarditis or rhabdomyolysis, or
 Invasive secondary bacterial infection based on
laboratory testing or clinical signs (eg, persistent high
fever and other symptoms beyond 3 days).

34. COMPLICATIONS
 Pulmonary complications:
 1. pneumonia
A. primary influenza viral pneumonia
least common but most severe
persistant fever, dyspnea, and cyanosis.
scanty sputum with few physical signs
chest x-ray : diffuse interstial infiltrates and or ARDS.
 B. secondary bacterial pneumonia
persistant fever
cough with production of purulent sputum, physical
signs and xray signs of consolidation.
most common bacterial pathogens- st. pneumonia,
staph. Aureus, and haemophilus influenzae.
respond to antibiotic therapy.

35.  C. Mixed viral and bacterial pneumonia
most common pneumonic complication during
outbreaks.
sputum cultures – both influenza A and bacterial
pathogen involved
CXR- patchy infiltrates or areas of consolidation
respond to appropriate antibacterial and antiviral drugs.
2. Exacerabation of COPD and Br. Asthma.
Extrapulmonary complications :
Myositis, Rhadomyolysis, Myoglobinuria
Myocarditis , & pericarditis
Encephalitis , transverse myelitis , GB Syndrome.
Toxic shock syndrome
Reye’s syndrome ( after aspirin use in flu)

37.  In order to prevent and control outbreak of Influenza-
A H1N1 virus for screening, testing and isolation
following guidelines are to be followed:
 All individuals seeking consultations for flu like
symptoms should be screened at healthcare facilities
both Government and private or examined by a
doctor and these will be categorized as under:
Category – A
Category -- B
Category -- C

38. Category- A
 Patients with mild fever plus cough / sore throat with
or without body ache, headache, diarrhoea and
vomiting will be categorized as Category-A.
 They do not require Oseltamivir and should be
treated for the symptoms mentioned above. The
patients should be monitored for their progress and
reassessed at 24 to 48 hours by the doctor.
 No testing of the patient for H1N1 is required.
 Patients should confine themselves at home and
avoid mixing up with public and high risk members in
the family.

39. Category-B
 In addition to all the signs and symptoms mentioned
under Category-A, if he patient has high grade fever
and severe sore throat, may require home isolation and
Oseltamivir;
 In addition to all the signs and symptoms mentioned
under Category-A, individuals having one or more of
the following high risk conditions shall be treated with
Oseltamivir. (patients with mild illness but with
predisposing risk factors like lung diseases, heart
disease, liver disease, kidney disease, blood disorders,
diabetes, neurological disorders, cancer and HIV/AIDS;
Patients on long term cortisone therapy.)
 No tests for H1N1 is required for Category-B
 All patients of Category-B should confine themselves at
home and avoid mixing with public and high risk
members in the family.

40. Category-C
 In addition to the above signs and symptoms of
Category-A and B, if the patient has one or more of the
following:
 Breathlessness, chest pain, drowsiness, fall in blood
pressure, sputum mixed with blood, bluish
discolouration of nails
 Worsening of underlying chronic conditions.
 All these patients mentioned above in Category-C
require testing, immediate hospitalization and
treatment.

41. Emergency warning signs
 Difficulty breathing or shortness of breath
 Pain or pressure in the chest or abdomen
 Sudden dizziness
 Confusion
 Severe or persistent vomiting

42. Diagnosis:
 Routine investigations required for evaluation and
management of a patient with symptoms as
described above will be required.
 These may include :
Haematological,
Biochemical,
Radiological and
Microbiological tests as necessary.

43.  CBC count and electrolytes assessment are nonspecific but
helpful -> Leukopenia and relative lymphopenia are typical.
 Thrombocytopenia may be present.
 Biochemical: raised hepatic enzymes
 Radiological: pneumonia
 Confirmation of Pandemic influenza A(H1N1) infection is
through: (clinical specimens such as nasopharyngeal swab,
throat swab, nasal swab, wash or aspirate, and tracheal
aspirate are to be obtained )
 -Real time RT PCR or
 -Isolation of the virus in culture or
 -Four-fold rise in virus specific neutralizing antibodies

44. Real Time PCR
 The kit utilizes a 3-module design and can:
 Identify and distinguish between influenza A and
B viruses,
 Classify influenza A viruses by subtype, and
 Detect highly pathogenic avian influenza A
(H5N1) virus infection in human respiratory tract
specimens.

45. Sample collection
 The sample should be collected by a trained physician /
microbiologist preferably before administration of the anti-viral
drug.
 Swab with synthetic tip made of calcium alginate is ideal
 Cotton or wooden sticks are not acceptable
 Obtain specimen within 5 days of symptoms onset
 Keep specimens at 4°C in viral transport media until transported
for testing.
 The samples should be transported to designated laboratories
with in 24 hours.
 If they cannot be transported then it needs to b stored at -70°C.
 Paired blood samples at an interval of 14 days for serological
testing should also be collected.
 Immunocompromised pts. May shed virus for weeks to months.

47. Indicators of poor prognosis
 Elevated alkaline phosphatase
 Elevated creatine kinase
 Thrombocytopenia

48. Treatment
 Supportive measures
 Antiviral drugs

49. Supportive measures:
 Increase liquid intake like water, juice, and soups.
 Rest for the 7 to 10 days during which the
symptoms may persist.
 Anti-pyretics.
 If patients begin taking antiviral drugs within 48
hours after their symptoms begin, the drugs may
reduce the length of the illness by about 1 to 2
days.

50. Anti-viral drugs:
General background
 All anti-viral drugs inhibit viral replication but they
act in different ways to achieve this.
 Drugs that are effective against influenza A
viruses: amantadine and rimantadine.
 Drugs that are effective against influenza A
viruses and influenza B viruses: zanamivir and
oseltamivir.

52. Oseltamivir and zanamivir
 These drugs are neuraminidase inhibitors.
 They prevent the NA proteins on the surface of the IV
from removing sialic acid from sialic acid-containing
receptors.
 Viral budding and downstream replication of IV are
inhibited when sialic acid remains on the virion
membrane and host cell.

53. Neuraminidase inhibition

54. As of January 2010, the antiviral
susceptibilities of circulating viruses
are:

55. Oseltamivir (Tamiflu)
 By inhibiting viral neuraminidase, decreases release of
viruses from infected cells and thus viral spread.
 Effective to treat influenza A or B.
 Start within 48h of symptom onset.
 Available as 30-mg, 45-mg, and 75-mg oral capsules
and as a powder for suspension that contains 12
mg/mL after reconstitution

56. Dosage
 Dose for treatment is as follows:
By Weight:
 For weight <15kg :30 mg BD for 5 days
 15-23kg: 45 mg BD for 5 days
 24-<40kg :60 mg BD for 5 days
 >40kg :--75 mg BD for 5 days

57. Prophylaxis dosage
 H1N1 Influenza A (Swine Flu) Prophylaxis
 75 mg PO qDay
 Postexposure prophylaxis: Initiate within 7 days of
exposure and continue for at least 10 days
 For community outbreak, may administer for up to 6
weeks

58.  Vomitings & nausea
 Occasionally -bronchitis, insomnia and
vertigo,angina, pseudo membranous colitis
 epistaxis, bronchitis, otitis media, dermatitis and
conjunctivitis have also been observed
 Rare: anaphylaxis and skin rashes.
 no recommendation for dose reduction in
patients with hepatic disease
Adverse reactions

59. Dosing Modifications
Renal impairment (CrCl 10-30 mL/min)
Prophylaxis: 75 mg PO qOD, OR 30 mg PO qDay
Treatment: 75 mg PO qDay x5 days
Renal impairment (CrCl <10 mL/min)
Administer with caution

60. Zanamivir (Relenza)
 Effective against both influenza A and B.
 Inhaled through Diskhaler oral inhalation device. Circular
foil discs containing 5-mg blisters of drug are inserted into
supplied inhalation device.
 Individuals with asthma or other respiratory conditions
that may decrease ability to inhale, the drug should be
given - Oseltamivir (eg, asthma, pregnancy).

61. Dosage
 Influenza A & B, Treatment
 Start within 2 days of symptom onset; administer 2 doses
on day 1, at least 2 hours apart
 10 mg inhaled q12hr for 5 days; may consider longer
treatment for patients severely ill after 5 days.
 Influenza A & B, Prophylaxis
 Household setting: 10 mg inhaled qDay for 10 days
 Initiate within 36 hours of exposure
 Community outbreaks: Begin within 5 days of outbreak;
may administer for up to 28 days

62.  Adverse Effects >10%
 Headache (13-24%)
 Throat/tonsil pain (8-19%)
 Cough ( 7-17%)
 Viral infection (3-13%)

63. Peramivir
Rapivab(investigational)
 Investigational neuraminidase inhibitor.
 Emergency-use authorization issued by US FDA for use
of peramivir in hospitalized adult pts. with suspected or
laboratory-confirmed 2009 H1N1 influenza
unresponsive to oseltamivir or zanamivir, unable to
take PO or inhaled drugs (or delivery route not
dependable or feasible), or other circumstances
determined by clinician.
 Mechanism of Action
 Elicits antiviral activity by inhibiting influenza virus
neuraminidase, an enzyme that releases viral particles
from the plasma membrane of infected cells
CDC-INFO (232-4636).

64.  Indicated for treatment of acute uncomplicated
influenza in patients aged: 18 yr who have been
symptomatic for not more than 2 days
 600 mg IV as a single dose
 Infuse diluted IV over 15-30 minutes
 Adverse Effects (1-10%)
 Diarrhea (8%),Neutrophils <1 x 10^9/L (8%).
 Increased serum glucose (>160 mg/dL) (5%).
 Creatine phosphokinase (≥6 xULN) (5%).
 Constipation (4%).Insomnia (3%).AST and ALT increased
(3%).Hypertension (2%)

65.  Renal impairment
 CrCl 30-49 mL/min: 200 mg IV as a single dose
 CrCl 10-29 mL/min: 100 mg IV as a single dose
 Pregnancy & Lactation
 Pregnancy category C; No data available for use
during pregnancy
 Lactation: unknown whether distributed in breast
milk

69. CDC recommends
 The following actions when human infection with H1N1
influenza (swine flu) is confirmed in a community :
 Patients who develop flulike illness (ie, fever with either
cough or sore throat) should be strongly encouraged to self-
isolate in their home for 7 days after the onset of illness or at
least 24 hours after symptoms have resolved, whichever is
longer.
 To seek medical care, patients should contact their health
care providers to report illness (by telephone or other
remote means) before seeking care at a clinic, physician's
office, or hospital.
 Patients who have difficulty breathing or shortness of breath
or who are believed to be severely ill should seek
immediate medical attention.

71. Vaccine formulations
 Vaccine formulations — two different types of influenza
vaccine are available,
inactivated influenza vaccines (IIVs) and a
live-attenuated influenza vaccine (LAIV)
 Trivalent influenza vaccines contain three different
vaccine viral antigens, one each from an influenza A
(H1N1) virus, an influenza A (H3N2) virus, and an influenza B
virus.
 Quadrivalent influenza vaccines contain the same three
antigens as trivalent vaccines, along with an antigen from
a second influenza B vaccine virus strain.
 Persons with a history of mild allergy to egg (specifically,
those who experience only hives) should receive IIV with
additional precautions.

72. Available FDA-approved vaccines
 Standard-dose trivalent and quadrivalent
-inactivated influenza vaccines
 The standard-dose inactivated influenza vaccines
are approved by the FDA for intramuscular
injection in adults of any age.
 These vaccines are produced in embryonated
chicken eggs.
 During the 2014 to 2015 influenza season, both
quadrivalent and trivalent formulations of
inactivated vaccines are available.

73.  Standard-dose quadrivalent LAIV – The intranasally
administered live-attenuated influenza vaccine (FluMist)
is approved for healthy nonpregnant adults up to 49
years of age.
 The vaccine is produced in embryonated chicken eggs.
Starting in the 2013 to 2014 influenza season, only a
quadrivalent formulation of LAIV is available;
 during previous seasons, LAIV was a trivalent vaccine.

74.  High-dose trivalent inactivated influenza vaccine — An
intramuscular high-dose inactivated influenza vaccine
(Fluzone high-dose) is approved for individuals ≥65 years
of age;
 the vaccine contains 60 mcg of each vaccine antigen
instead of 15 mcg, which is the standard dose
 Intradermal low-dose trivalent and quadrivalent
inactivated influenza vaccine — An intradermal
formulation of the inactivated influenza vaccine (Fluzone
intradermal) is approved for individuals between 18 and
64 years of age .
 It is supplied in a single-dose, preservative-free syringe.
 In late 2014, a quadrivalent formulation was approved by
the FDA .
 For the 2014 to 2015 influenza season, only the trivalent
formulation is available. The quadrivalent formulation is
expected to be available for the 2015 to 2016 influenza
season.

75.  Trivalent inactivated influenza vaccine produced in
cultured cells — A trivalent inactivated influenza vaccine
produced in cultured mammalian cells (Flucelvax) is
approved for individuals ≥18 years of age
 Trivalent inactivated influenza vaccine produced using
recombinant DNA technology and a baculovirus
expression system — A trivalent recombinant
hemagglutinin influenza vaccine (Flublok), that
produces virus-like particles, is approved for individuals
18 years of age or older

76. Choice of vaccine formulation
 The choice of vaccine formulation depends upon several
factors, including age, comorbidities, pregnancy, and risk
of adverse reactions
 For healthy nonpregnant adults up to 49 years of age,
prefer either a quadrivalent inactivated vaccine or LAIV
 For all individuals ≥50 years of age and for individuals with a
contraindication to receiving LAIV (eg,
immunocompromise; chronic cardiovascular, pulmonary,
or metabolic disease; pregnancy; severe allergy to an
influenza vaccine or its components; egg allergy),
recommends an inactivated influenza vaccine.
 Favor a quadrivalent formulation over a trivalent
formulation when possible.
 Individuals between 18 and 64 years of age can receive an
intradermal formulation of the trivalent inactivated
influenza vaccine (Fluzone intradermal).

77.  For individuals ≥65 years of age, suggest the
intramuscular high-dose trivalent inactivated influenza
vaccine (Fluzone high-dose) when available rather than
a standard-dose inactivated vaccine.
 Recommendations for individuals with egg allergy, two
vaccine formulations that are not produced in eggs are
available (Flublok and Flucelvax).

78.  Pregnancy — recommends the inactivated influenza
vaccination for pregnant women, regardless of the
stage of pregnancy, and of women who might be
pregnant during the influenza season.
 Immunocompromised hosts — The ACIP recommends
the inactivated influenza vaccine for
immunocompromised patients, including HIV-infected
individuals, patients with cancer, and transplant
recipients.
 LAIV is contraindicated in immunocompromised
individuals

81.  VAXIGRIP is a sterile suspension of influenza virus for
intramuscular or deep subcutaneous injection.
 It is a purified, inactivated, split virion vaccine.
 VAXIGRIP contains the following strains of influenza virus:
 A/California/7/2009 NYMC X-179A (A/California/7/2009
[H1N1]pdm09 -like),
 A/Victoria/361/2011 IVR-165 (A/Victoria/361/2011 [H3N2] –
like), and
 B/Hubei-Wujiagang/158/2009 NYMC BX-39
(B/Wisconsin/1/2010 - like)

83. COMPOSITION:
Each 0.5 mL dose contains:
Purified 15 mcg Haemagglutinin Antigen of
A/California/7/2009
H1N1 Influenza NIBRG-121xp virus in Phosphate Buffered
Isotonic Sodium Chloride Solution
50 mcg Thiomersal added as a preservative
The H1N1 virus strain is propagated in allantoic fluid of hen’s
egg and inactivated by β—propiolactone.
Single dose: 0.5 ml / Vial
Multi dose: 5 ml / Vial
Vaccine for intramuscular injection
Shelf life 24 months.
Store between 2-8 °C. Do not freeze.

85. NASOVAC-S, Influenza Vaccine, (Human), freeze dried is a live
trivalent vaccine for administration by intranasal spray. NASOVAC-
S contains three vaccine virus strains of A/H1N1, A/H3N2 and Type
B influenza virus cultivated on embryonated hen eggs.
The three strains are antigenically similar to the strains
recommended by the World Health Organization (W.H.O.) for 2014
INDICATIONS
NASOVAC-S is indicated in individuals above 2 years of age
A dose of 0.5 ml is administered as 0.25 ml per nostril using a 1.0
ml syringe and a spray device. The spray device creates a fine
spray that primarily deposits the vaccine in the nose and
nasopharynx.

86.  CAUTION: PEOPLE WHO SHOULD NOT TAKE THE
VACCINE
 1.Those who are allergic to eggs
 2 .Children and adolescents (2-17 years of age)
receiving aspirin and aspirin containing therapy.
 People already suffering from cold, cough, fever,
bodyache or other flu-like symptoms should be clinically
evaluated and if necessary, appropriate treatment
should be given. In such cases, NASOVAC-S
vaccination should be postponed at least till recovery.

87. Adverse reactions of vaccines
 Inactivated vaccines — The inactivated influenza
vaccines are generally well tolerated, with the most
common side effect being arm soreness at the injection
site
 A slightly increased risk of Guillain-Barré syndrome
 The intradermal inactivated influenza vaccine has been
associated with higher rates of injection site reactions
(erythema, induration, swelling, and pruritus, but not pain)
 Needle-free intramuscular administration — of a trivalent
IIV (Afluria) with a jet injector device is associated with a
higher frequency of local injection site reactions than the
use of needle and syringe
 Intranasal vaccine — The LAIV is generally well tolerated,
with the most common side effects in adults being
rhinorrhea, nasal congestion, headache, and sore throat

88. Contraindications to vaccination
 contraindicated in patients who have had a
severe allergic reaction (eg, anaphylaxis) to an
influenza vaccine or its components.
 Recommendations for individuals with egg allergy
 individuals who developed Guillain-Barré
syndrome within six weeks after a previous
influenza immunization.

89.  LAIV should not be given to:
 Immunocompromised patients and those with
immunosuppression
 Pregnant women
 Adults aged ≥50 years
 Persons with a history of egg allergy
 Individuals who have taken an influenza antiviral
medication within the previous 48 hours
 Healthcare workers and household members who have
close contact with severely immunocompromised persons
who require a protective environment should not receive
LAIV or should avoid contact with such patients for seven
days after receipt

90.  For adults and older children, the recommended
site of vaccination is the deltoid muscle.
 The preferred site for infants and young children is
the anterolateral aspect of the thigh.

91. Schedule
 Outbreaks of influenza generally occur during the
winter months (which occur at different times of
the year).
 A single dose of an influenza vaccine should be
administered to adults annually and offered soon
after the vaccine becomes available, ideally by
October
 Repeat vaccination is not necessary in those who
received routine vaccination at the appropriate
time in the previous fall or winter.

93. PPE (Personal Protection Equipments)
 Standard Operating Procedures on Use of PPE Personal
Protection Equipments PPE reduces the risk of infection
if used correctly. It includes:
 Gloves (nonsterile),
 Mask (high-efficiency mask) / Three layered surgical
mask (N-95)
 Long-sleeved cuffed gown,
 Protective eyewear (goggles/visors/face shields),
 Cap (may be used in high risk situations where there
may be increased aerosols)
 Plastic apron if splashing of blood, body fluids,
excretions and secretions isanticipated.

98. References
 HARRISON’S PRINCIPLES OF INTERNAL MEDICINE – Chapter
INFLUENZA – page no 1493 – 1499.
 API TEXT BOOK OF MEDICINE, chapter – swine flu & bird flu –
page no 1155-1157.
 MEDICINE UPDATE VOL. 23, 2013, chapter 9, page no 34-37.
 PROGRESION IN MEDICINE – VOL. 2015, chapter 35 –
influenza fever , page no.345- 353.
 FEVER – a practical guide, chapter swine flu- page no 53-
58.
 United States Centers for Disease Control and Prevention.
Interim guidance on case definitions to be used for
investigations of novel influenza A (H1N1) cases
http://www.cdc.gov/h1n1flu/casedef.htm.

99.  United States Centers for Disease Control and Prevention.
Updated interim recommendations for the use of antiviral
medications in the treatment and prevention of influenza for the
2009-2010 season.
http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed
on December 15, 2009).
 Papenburg J, Baz M, Hamelin MÈ, et al. Household transmission of
the 2009 pandemic A/H1N1 influenza virus: elevated laboratory‐
confirmed secondary attack rates and evidence of
asymptomatic infections. Clin Infect Dis 2010; 51:1033.
 Cheng VC, To KK, Tse H, et al. Two years after pandemic
influenza A/2009/H1N1: what have we learned? Clin Microbiol
Rev 2012; 25:223.
 Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team,
Dawood FS, Jain S, et al. Emergence of a novel swine-origin
influenza A (H1N1) virus in humans. N Engl J Med 2009; 360:2605.
 World Health Organization. Human infection with new influenza A
(H1N1) virus: clinical observations from Mexico and other
affected countries, May 2009
http://www.who.int/wer/2009/wer8421.pdf (Accessed on
October 13, 2011).

100.  Louie JK, Acosta M, Winter K, et al. Factors associated with death or
hospitalization due to pandemic 2009 influenza A(H1N1) infection in
California. JAMA 2009; 302:18
 Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with
2009 H1N1 influenza in the United States, April-June 2009. N Engl J
Med 2009; 361:1935.
 Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al.
Pneumonia and respiratory failure from swine-origin influenza A
(H1N1) in Mexico. N Engl J Med 2009; 361:680.96.
 Muscedere J, Ofner M, Kumar A, et al. The occurrence and impact
of bacterial organisms complicating critical care illness associated
with 2009 influenza A(H1N1) infection. Chest 2013; 144:39.
 ANZIC Influenza Investigators, Webb SA, Pettilä V, et al. Critical care
services and 2009 H1N1 influenza in Australia and New Zealand. N
Engl J Med 2009; 361:1925.
 United States Centers for Disease Control and Prevention. Interim
Recommendations for Clinical Use of Influenza Diagnostic Tests
During the 2009-10 Influenza Season
 United States Centers for Disease Control and Prevention. Interim
guidance for the detection of novel influenza A virus using rapid
influenza diagnostic tests

101. Thank you