H1N1 Influenza (Swine Flu)

CHAIRPERSON: DR. P.V. VENKATARAMANAPPA PRESENTER: DR. M. RAMESH BABU M.V.J. MEDICAL COLLEGE

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

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.

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.

Current scenario 2015

INFUENZA

Orthomyxoviruses -pleomorphic Irrerugar spherical 80-120 nm in diameter

ORTHOMYXOVIRUS

Influenza SubtypesTypes A & B 3 IMPs HA NA M28 Segments of RNAResponsible for epidemics & pandemics

Type C 1 IMP HEFServes functions of both HA and NA7 Segments of RNACauses 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

There are 16 Hemagglutinin ( H ) antigens 1 to 16 Neuraminidase ( N ) antigens 1 to 9All 16 (H) subtypes of influenza A viruses readily infect the

birdsviruses having any of the H1, H2, H3 antigens and any of

the N1 or N2 antigens only infect humansH1N1, 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.

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.

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

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

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

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.

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

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

VIRUS

CLEARANCE OF VIRUSIMMUNITY

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)..

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

Proposed Mechanism of the Cytokine Storm Evoked by Influenza virus:

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

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

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).

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.

DEFINITIONS OF ILLNESS SEVERITY

Mild or uncomplicated illness : is characterized byfever, 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.

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).

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).

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.

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, MyoglobinuriaMyocarditis , & pericarditisEncephalitis , transverse myelitis , GB Syndrome.Toxic shock syndromeReye’s syndrome ( after aspirin use in flu)

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

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.

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.

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.

Emergency warning signs

Difficulty breathing or shortness of breath Pain or pressure in the chest or abdomen Sudden dizziness Confusion Severe or persistent vomiting

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.

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

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.

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.

Indicators of poor prognosis

Elevated alkaline phosphatase

Elevated creatine kinase

Thrombocytopenia

Treatment

Supportive measures Antiviral drugs

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.

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.

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.

Neuraminidase inhibition

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

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

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

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

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

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

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).

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

Adverse Effects >10%

Headache (13-24%)

Throat/tonsil pain (8-19%)

Cough ( 7-17%)

Viral infection (3-13%)

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).

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%)

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

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.

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.

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.

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.

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.

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

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).

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).

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

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)

COMPOSITION:Each 0.5 mL dose contains:Purified 15 mcg Haemagglutinin Antigen of A/California/7/2009H1N1 Influenza NIBRG-121xp virus in Phosphate Buffered Isotonic Sodium Chloride Solution50 mcg Thiomersal added as a preservativeThe H1N1 virus strain is propagated in allantoic fluid of hen’s egg and inactivated by β—propiolactone.Single dose: 0.5 ml / VialMulti dose: 5 ml / Vial Vaccine for intramuscular injectionShelf life 24 months. Store between 2-8 °C. Do not freeze.

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 INDICATIONSNASOVAC-S is indicated in individuals above 2 years of ageA 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.

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.

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

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.

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

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.

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.

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.

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Thank you