management of influenza
TRANSCRIPT
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