6. Influenza A Subtypes:
-Based on:
Hemagglutinin (HA)
H1 to H16
Neuraminidase (NA)
N1 to N9
144 different combinations
7.
8.
9. Wild birds are “natural” reservoir for all
influenza A subtypes
10. Natural hosts of influenza viruses
Haemagglutinin subtype Neuraminidase subtype
H 1
H 2
H 3
H 4
H 5
H 6
H 7
H 8
H 9
H 10
H 11
H 12
H 13
H 14
H 15
H 16
N 1
N 2
N 3
N 4
N 5
N 6
N 7
N 8
N 9
12. The subtypes of influenza A viruses currently circulating
among humans as seasonal influenza strains are :
influenza A(H1N1) and A(H3N2) subtypes.
Circulating influenza B viruses can be divided into 2 main
groups (lineages), referred to as B/Yamagata & B/Victoria
lineages. Influenza B viruses are not classified into
subtypes.
13. Influenza A and B viruses circulate and cause seasonal
outbreaks and epidemics. Due to this reason, relevant
strains of influenza A and B viruses are included in
seasonal influenza vaccines.
Influenza type C virus is detected much less frequently&
usually causes mild infections, thus presents less
significant public health implications.
14.
15.
16. 16
Fever
Cough
Sore throat
Muscle pain
Malaise
No dyspnea and
shortness of breath
GIT symptom may also
present
Shortness of breath and
dyspnea
Lower RTI ( pneumonia )
CNS involvement
Severe dehydration
Secondary complications
COPD – asthma
exacerbation
• Complicated
influenza
• Uncomplicated
influenza
17. Seasonal influenza epidemics can cause febrile illnesses
that range in severity from mild to debilitating and can
lead in some instances to hospitalization and even
cause death, mainly among high-risk groups.
Seasonal influenza is a serious public health problem, it
has been estimated that in developed countries, annual
influenza epidemics infect about 10–20% of the general
population each season .
18. Symptoms are similar for influenza A and B viruses, most
people recover from fever and other symptoms within a
week without requiring medical attention. But influenza
can cause severe illness or death especially in people
at high risk .
Worldwide, annual influenza epidemics are estimated to
result in ~1 billion cases of flu, ~3–5 million cases of
severe illness and 300 000–500 000 deaths annually.
19. Who is at risk?
oSeasonal influenza epidemics can seriously affect all
populations, but the highest risk of complications occur
among pregnant women, children aged 6–59 months, the
elderly, individuals with specific chronic medical conditions
or immunocopromised patients and health-care workers.
oSevere disease may also occur in otherwise healthy children
and young adults.
23. Diagnosis and Management
oInfluenza testing is not needed for all patients with signs
& symptoms of influenza to make antiviral treatment
decisions.
oIn general, in the context of a community outbreak of
influenza, testing for influenza is not indicated.
oIf testing is done, it is recommended that RT-PCR
(Reverse Transcriptase Polymerase Chain Reaction) tests
be performed from throat swabs, nasopharygeal swabs.
24. oInfluenza testing is appropriate for hospitalized inpatients,
especially if a positive test would result in a change in
clinical management.
oThe clinical diagnosis of influenza can be made for outpatients
with signs and symptoms consistent with influenza , results of
diagnostic testing are not available in a timely manner to
inform clinical decision making.
oThe use of rapid tests is not recommended, due to their low
sensitivity.
25. oWhen influenza viruses are known to be circulating
in a community , patients presenting with features
of uncomplicated influenza with or without high risk
factors of developing severe or complicated illness
can be diagnosed on clinical & epidemiological
grounds, will not rquire influenza laboratory
confirmation.
26. oPatients with mild influenza like illness who present with
an uncomplicated febrile illness typically do not require
antiviral treatment unless they are at higher risk for
serious influenza complications.
oPatients with complicated or severe influenza like illness
should be hospitalized & treated with antivirals .
27. Antiviral treatment is recommended as early as possible
for any patient with confirmed or suspected influenza
who :
1. is hospitalized
2. has severe, complicated, or progressive illness
3. is at higher risk for influenza complications.
4. Most people who are otherwise healthy and get the
flu do not need to be treated with antiviral drugs .
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41. Adamantanes and Rimantadine are M2 ion channel
blockers; they interfere with hydrogen ion channel
activity of the influenza A virus and prevent viral
uncoating.
M2 proton channel blockers protect only against the A
viruses, however they are ineffective against all
currently circulating influenza virus strains.
42.
43.
44.
45.
46. • As new viruses emerge from the host cell, they are coated
in a layer of glycolipid originating from the cell membrane.
• Haemagglutinin receptors from the virus are bound to these
glycolipids.
• Neuraminidase cleaves the glycolipid from the haemagglutinin
thus releasing the virus completely from the host cell.
47.
48.
49. oNeuraminidase, an enzyme, breaks the bonds that hold
new virus particles to the outside of an infected cell.
oOnce the enzyme breaks these bonds, this sets free new
viruses that can infect other cells and spread infection.
oNeuraminidase inhibitors block the enzyme's activity &
prevent new virus particles from being released, thereby
limiting the spread of infection.
50. Neuraminidase inhibitors block viral neuraminidase enzyme,
which is critical in releasing virions from the infected host's
cells. These drugs are active against influenza A and B.
Neuraminidase inhibitors,are not cures and do not kill the virus
but interfere with the way the virus multiplies , they shorten flu
episodes by a couple of days, reduce the risk of complications
and possibly lower the likelihood that someone will pass on
the virus.
Ideally, they should be given as early as possible especially
within 48 hours of influenza illness onset.
51. Neuraminidase inhibitors do not ‘kill’ the flu virus but
merely slow the virus replication down to a level where
the immune system can more easily destroy it.
Thus they can reduce the severity and duration of a flu
illness.
Neuraminidase inhibitors are effective against all strains
of influenza A, unlike vaccines which are specific only
to the strains for which they were designed.
52. There are three FDA-approved influenza antiviral drugs
(Neuraminidase inhibitors) recommended by CDC this
season to treat influenza:
1. Oseltamivir (trade name Tamiflu®)
2. Zanamivir (trade name Relenza®)
3. Peramivir (trade name Rapivab®).
53. Due to high levels of resistance , Amantadine and
Rimantadine are not recommended for antiviral treatment or
chemoprophylaxis of currently circulating influenza A viruses
WHO recommends neuraminidase inhibitors as the first-
line treatment for people requiring influenza antiviral
therapy.
54.
55. Antiviral resistance to oseltamivir, zanamivir, and
peramivir among circulating influenza viruses is
currently low, but this can change.
57. Clinical judgment is important when making antiviral
treatment decisions.
Decisions to start antiviral treatment should not wait for
laboratory confirmation of influenza because laboratory
testing can delay treatment and because a negative rapid
influenza diagnostic test result does not rule out influenza .
58. When indicated, Clinical benefit is greatest when antiviral
treatment is administered early, ideally within 48 hours of
influenza illness onset.
Clinical trials & observational data show that early antiviral
treatment can shorten the duration of fever and illness
symptoms, and may reduce the risk of complications
from influenza .
59. Antiviral treatment for influenza might have benefits in
patients with severe, complicated or progressive illness,
and in hospitalized patients even when started after 48
hs of illness onset (up to 4 or 5 days after illness onset).
60. For outpatients with uncomplicated influenza :
Oral oseltamivir, inhaled zanamivir, or intravenous peramivir
may be used for treatment.
The recommended treatment course for uncomplicated
influenza is two doses per day of oral oseltamivir or inhaled
zanamivir for 5 days, OR one dose of intravenous peramivir
for 1 day.
.
61.
62. For hospitalized patients and patients with severe or
complicated illness, treatment with oral or enterically
administered Oseltamivir is recommended.
Inhaled Zanamivir is not recommended because of the lack of
data for use in patients with severe influenza disease.
There is also insufficient data regarding efficacy of intravenous
Peramivir for hospitalized patients..
63. The optimal duration and dosing are uncertain for severe
or complicated influenza.
Treatment regimens might need to be altered to fit the
clinical circumstances. For example, clinical judgment
should be the guide regarding the need to extend daily
treatment regimens longer than 5 days for patients
whose illness is prolonged.
64. A higher dose of oral or enterically administered oseltamivir
has been recommended by (e.g.150 mg twice daily in adults
with normal renal function) for the treatment of influenza in
immunocompromised patients & in severely ill hospitalized
patients.
65. Hospitalized patients with suspected influenza should
be treated empirically with Neuraminidase Inhibitors,
which will provide protection, effective against both
influenza A & B viruses .
Oseltamivir is the recommended first- line antiviral
agent for neuraminidase-sensitive influenza virus
infection,ideally initiated within 48 hours of symptom
onset.
66. Clinicians should realize that a negative RIDT result does NOT
exclude a diagnosis of influenza in a patient with suspected
influenza.
When there is clinical suspicion of influenza and antiviral
treatment is indicated, antiviral treatment should be started as
soon as possible without waiting for results of additional
influenza testing.
Follow-up negative results with confirmatory tests (i.e.,RT-PCR
or viral culture) if a laboratory-confirmed influenza diagnosis is
desired.
67. • All patients with complicated influenza should receive
treatment, often in hospital.
• Treatment should be started as early as possible; do
not wait for laboratory confirmation of influenza virus
infection.
• The duration of therapy depends on clinical response.
68. Patients with severe, progressive or complicated illness
consistent with a diagnosis of influenza should be treated
empirically with neuraminidase inhibitors as soon as possible
, irrespective of the presence of underlying comorbidities &
even if the time elapsed between symptom onset and first
opportunity to treat is >48hrs.
69. Do not delay initiation of oseltamivir treatment while waiting
for influenza testing results.
Clinical judgment is an important factor in antiviral treatment
decisions.
Evidence indicates that the greatest benefit is derived from
early oseltamivir treatment. Therefore, suitable preparations
of oseltamivir need to be available at the point of care.
70. Clinicians should consider influenza virus infection as a
possible cause of any febrile respiratory illness requiring
hospitalization during influenza season and consider
testing for influenza and starting empiric antiviral therapy
& Do not wait for laboratory confirmation of diagnosis.
71.
72.
73.
74.
75.
76. Pharmacokinetics & Absorption:
• Oseltamivir is absorbed from the gastrointestinal tract after
oral administration & is extensively converted predominantly
by hepatic esterases to the active metabolite.
• Neither oseltamivir nor its active metabolite (Oseltamivir
carboxylate) are substrates for or inhibitors of cytochrome
P450 isoforms.
• Plasma concentrations of active metabolite are proportional to
dose and are not significantly affected by co-administration
with food
77. • The capsules and oral suspension may be taken with or
without food; however, tolerability may be enhanced if
Tamiflu is taken with food.
• Excretion: The active metabolite is not further metabolized
and is eliminated in the urine.
•
78. Drug interaction
• Clopidogrel (Plavix) decreases serum concentrations
levels of active metabolite(s) of oseltamivir (Tamiflu).
• Tamiflu must be hydrolyzed in the body to be effective..
But in the presence of clopidogrel , the hydrolysis of
Tamiflu was inhibited as much as 90 percent,
• "Concurrent use of both drugs would inhibit the activation
of oseltamivir , thus making this anti-viral agent
therapeutically inactive.“
79. Oseltamivir administered orally or by oro/naso gastric
tube is well absorbed in critically ill influenza patients,
including those in the intensive care unit, on continuous
renal replacement therapy, and/or on extracorporeal
membrane oxygenation
Intubated patients with influenza illness should receive
oseltamivir through a nasogastric tube .
80. Children over one year of age and adults with swallowing
difficulties, and those receiving nasogastric oseltamivir,
should use capsules which are opened and mixed into
an appropriate sugary liquid as oseltamivir has a very
bitter taste.
81. o Oseltamivir and Zanamivir are "Pregnancy Category C"
medications .
o No adverse effects have been reported among women
who received Oseltamivir or Zanamivir during pregnancy
or with their babies.
o When considering antiviral treatment, pregnancy should
not be considered as contraindication to Oseltamivir use.
Use of influenza antivirals in pregnancy
82. • Tamiflu is the treatment of choice for pregnant women.
Recommended for women at all stages of pregnancy
to prevent serious complications from the flu.
• Pregnant women should receive the same standard
dose regimen as adults for antiviral treatment.
• Also ,women can continue to breast-feed while being
treated with antivirals.
83. No dose adjustment is needed in obese patients either
for Oseltamivir or Zanamivir.
Studies indicate that the exposure to oseltamivir carboxylate
(the active metabolite of oseltamivir) is similar between
obese and non-obese subjects for both 75 mg and 150 mg
doses given twice daily.
84. • Dose modification of oseltamivir should be considered
in patients with impaired renal function as serum
concentrations of oseltamivir carboxylate, the active
metabolite of oseltamivir, will increase with declining
renal function .
• Duration of treatment and chemoprophylaxis is the same
as recommended for patients with normal renal function.
85. Dose adjustment of oseltamivir is recommended for patients
with creatinine clearance between 10 and 60 mL/min and
patients with end-stage renal disease (ESRD) undergoing
hemodialysis or continuous peritoneal dialysis receiving
oseltamivir for the treatment or chemoprophylaxis of
influenza.
Oseltamivir is not recommended for patients with ESRD not
undergoing dialysis.
86.
87. No dose adjustment is recommended for inhaled Zanamivir
for a 5-day course of treatment for patients with renal
impairment.
88.
89.
90.
91.
92. Inhaled zanamivir via Diskhaler® may not be an effective
delivery route in some patients, including those unable to
administer the Diskhaler® and patients with severe
underlying respiratory disease.
Inhaled zanamivir is not licensed for use in children less
than five years.
93. Zanamivir powder for inhalation should NOT be nebulised
by dissolving the capsules in water. This practice has been
linked to deaths in ICU believed to be due to blockage of
ventilator tubes.
The powder preparation for the Diskhaler® should NEVER
be made into nebuliser solution or administered to a
mechanically ventilated patient.
94.
95. • Transient neuropsychiatric events (self-injury or delirium)
have been reported postmarketing among persons taking
oseltamivir; the majority of reports were among Japanese
adolescents and adults .
• Several recent analyses and reviews have found that
oseltamivir is not associated with an increased risk for
neuropsychiatric events .
96.
97.
98.
99.
100.
101.
102. • Influenza is a major cause of severe respiratory infections
leading to excessive hospitalizations and deaths globally:
1) Annual epidemics (e.g., A/H3N2, A/H1N1, B; due to
antigenic drift)
1. 2) Pandemics (e.g., A/H1N1pdm09;due to antigenic shift -
genetic re-assortment)
2. 3) Sporadic/endemic avian Influenza virus infections
(e.g., A/H5N1, A/H7N9; adapted for limited human
transmission)
• Antivirals may improve viral clearance, shorten illness duration,
reduce complications, lower death risks, and reduce disease
transmission
103. Oseltamivir (Tamiflu®) is an orally administered antiviral for
the treatment and prevention of influenza A and B infections
that is registered in more than 100 countries worldwide.
More than 83 million patients have been exposed to the product
since its introduction.
Oseltamivir is recommended by the World Health Organization
(WHO) for use in the clinical management of pandemic and
seasonal influenza of varying severity, and as the primary
antiviral agent for treatment of avian H5N1 influenza
infection in humans.
Oseltamivir in Seasonal,Pandemic,Avian influenza
104.
105. Post exposure Chemoprophylaxis
According to the CDC, antiviral chemoprophylaxis generally
should be reserved for persons at higher risk for influenza-
related complications who have had contact with someone
likely to have been infected with influenza.
Antiviral chemoprophylaxis is not appropriate for healthy
children or adults based on potential exposure in the
community.
106. • The following are examples of situations where antiviral
medications can be considered for chemoprophylaxis
to prevent influenza
1. Prevention of influenza in persons at high risk of influenza
complications during the first two weeks following vaccination
after exposure to an infectious person.
2. Prevention for people with severe immune deficiencies who
might not respond to influenza vaccination,such as persons
receiving immunosuppressive medications, after exposure
to an infectious person.
3. Prevention for people at high risk for complications from
influenza who cannot receive influenza vaccine due to a
contraindication after exposure to an infectious person.
4. Prevention of influenza among residents of institutions, such
as long-term care facilities, during influenza outbreaks in the
institution.
107. Post exposure Chemoprophylaxis
Clinical judgment and advice from local authorities are
important factors in making postexposure chemoprophylaxis
decisions.
Post exposure Antiviral chemoprophylaxis is not generally
recommended if more than 48 hours have elapsed since the
last contact with an infectious person.
108. In areas with limited antiviral medication availability, local
public health authorities might provide additional guidance
about prioritizing chemoprophylaxis within groups at higher
risk for complications.
In certain situations, CDC or local public health authorities
might recommend that antiviral medication resources be
primarily directed at treatment and that chemoprophylaxis
be used only in certain limited situations.
109. Indiscriminate use of antiviral chemoprophylaxis might
promote resistance to antiviral medications or reduce
antiviral medication availability for treatment of persons at
higher risk for influenza complications or who are severely ill.
CDC does not recommend widespread or routine use of
antiviral medications for chemoprophylaxis so as to limit
the possibilities that antiviral resistant viruses could emerge.
110. Patients receiving postexposure antiviral chemoprophylaxis
should be informed that chemoprophylaxis lowers but does
not eliminate the risk for influenza, that susceptibility to
influenza returns once the antiviral medication is stopped,
and that influenza vaccination is recommended if available.
Chemoprophylaxis with antiviral medications is not a
substitute for influenza vaccination when influenza vaccine
is available .
111. Patients receiving chemoprophylaxis should be encouraged
to seek medical evaluation as soon as they develop a febrile
respiratory illness suggestive of influenza because influenza
virus infection still can occur while a patient is on antiviral
chemoprophylaxis .
112. • An emphasis on close monitoring and early initiation of
antiviral treatment (if fever and/or respiratory symptoms
develop) is an alternative to chemoprophylaxis in
managing certain persons who have had a suspected
exposure to influenza virus .
• Antiviral chemoprophylaxis is currently NOT recommended
by the WHO .
113. Duration of Chemoprophylaxis
• Postexposure chemoprophylaxis is typically administered
for a total of no more than 10 days after the most recent
known exposure to a close contact known to have
influenza
114.
115.
116. If there is a community or nosocommial outbreak of influenza,
Unvaccinated health-care workers who have occupational
exposures&who did not use adequate personal protective
equipment at the time of exposure are also potential
candidates for chemoprophylaxis
117. If an unvaccinated HCW is exposed to a patient with
influenza they should be immunized with TIV and offered
chemoprophylaxis with either osetamivir or zanamivir used
once daily.
For newly vaccinated HCW , antiviral chemoprophylaxis
can be administered up to 2 weeks following influenza
vaccination with TIV (until immunity after vaccination
develops).
118. • Influenza Vaccines and Use of Influenza Antiviral
Medications
• Administration of inactivated influenza vaccine to persons
receiving influenza antiviral drugs for treatment or
chemoprophylaxis is acceptable.
• Inactivated influenza vaccine can be administered at any
time relative to use of TAMIFLU.
119. • Live-attenuated influenza vaccine should not be administered
until 48 hours after cessation of influenza antiviral therapy.,
because antiviral drugs reduce & inhibit replication of live
vaccine virus and possibly reduce the efficacy of LAIV
• If influenza antiviral medications are administered within 2
weeks after receipt of live-attenuated influenza vaccine, the
vaccine dose should be repeated 48 or more hours after the
last dose of antiviral medication.
120. • Persons receiving antiviral chemoprophylaxis should not
receive live attenuated influenza virus vaccine (LAIV) &
persons receiving LAIV should not receive antiviral
treatment or chemoprophylaxis until 14 days after
LAIV administration.
121. • Oseltamivir is not a substitute for the flu shot. Continue to
receive an annual flu shot as advised by your doctor.
• Annual influenza vaccination is the best way to prevent
influenza because vaccination can be given well before
influenza virus exposures occur, and can provide safe&
effective immunity throughout the influenza season.
122. While influenza vaccination is the first and best way to
prevent influenza illness, a history of influenza vaccination
does not rule out the possibility of influenza virus infection
in an ill patient with clinical signs and symptoms compatible
with influenza.
A history of influenza immunisation does not exclude
influenza as a possible diagnosis.
