Dr Asif Hussain

JR-2

JNMCH, AMU

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.

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

Dyspnoea

Bluish discoloration of skin

Not drinking enough fluids

Severe or persistent vomiting

Not waking up or not interacting

Irritable

Flu-like symptoms

Birth to 4 years old

Pregnant women

>65 years old

Long-term aspirin therapy

Disorders of the pulmonary or cardiovascular system.

Metabolic diseases

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.

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).

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

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.

Samples Nasal swab/wash

Tracheal aspirate

Laboratory findings1. Leukopenia and/or lympopenia

2. Elevated Serum lactate dehydrogenase (LDH)

Management

Investigations:

Rapid antigen detection

Immunofluorescence

Nucleic acid test : rRT-PCR

Viral culture

Antibody testing

Supportive Isolation

Oxygen therapy

Intravenous hydration

Symptomatic relief

Critical care needs: ventilatator, hemodynamic support.

Antiviral therapy

Adjunct therapy:Prophylactic antibiotics

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

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

Inhibitors of viral penetration and uncoating

Amantadine

Rimantadine

Neuraminidase inhibitorsOseltamavir

Zanamavir

Peramivir

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

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.

Side effects include :

nervousness,

light-headedness,

difficulty concentrating,

insomnia, and

loss of appetite

Nausea & vominting

Ankle edema

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)

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

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

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

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

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

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

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

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

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

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.

Hand washing technique

Facemasks (disposable, single use masks) for persons who enter crowded settings

Respirators (N95 or higher filtering facepiecerespirator) 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

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

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

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