about influenza in this season

2. Important differential diagnosis of influenza
 During a community-wide outbreak, a clinical diagnosis of
influenza can be made with a high degree of certainty with
typical illness.
 In the absence of an outbreak (i.e., in sporadic or isolated
cases),influenza may be difficult to differentiate on clinical
grounds alone from an acute respiratory illness caused by any
of a variety of respiratory viruses or by Mycoplasma
pneumoniae.
 BACTERIAL PNEUMONIA-classical association between
pleuritic chest pain and productive cough.
 Notes-bact. Pneumonia can occur with concurrent viral
pneumonia or can be occurred upto 2wks post influenza.
Bacterial pneumonias generally do not run a self-limited course

3. d/d continued:
COMMODN COLD-upper respiratory symptoms dominated
with rhinitis. Fever is usually absent or mild.
 Notes-fever is a negative predictor rhinovirus infection in
adult.
STREPTOCOCCAL PHARYNGITIS: presence of tender
unilateral adenopathy with exudates is typical of strep
pharyngitis.
Notes-severe sore throat is not evidence of influenza.
BACTERIAL MENINGITIS OR ENCEPHALITIS:in general
present with clouded sensorium, headache, neck stiffness.
Notes- early presentation may be confused with influenza.
Most of the patients with influenza should have some
improvement within 48 hrs. influenza often associate with
invasive cns pathology.
OTHERS-febrile seizure, inhalational anthrax

4. DIAGNOSIS OF INFLUENZA:
 The diagnosis of influenza depends on epidemiologic,
clinical and laboratory considerations.
 LAB DIAGNOSIS-
• Clinical lab test are nonspecific for diagnosis of influenza.
• Relative LEUCOPENIA is frequently seen ,though it is
variable.
• If there is leucocytosis with count >15000,raised suspicion
of secondary bacterial infections.
• Chest X ray show evidence of atelectasis or infiltrate in 10%
of children
• In case of severe disease and bird flu there may be elevated
transaminase and LDH level

5. Specific diagnostic test for influenza:
PREFERRED SAMPLES
a) Nasopharyngeal swab
b) Nasal wash, aspirate or swab
c) Endotracheal aspirate
d) Bronchoalveolar lavage[BAL]
e) Oropharyngeal swab
f) Combined nasopharyngeal or nasal swab with
oropharyngeal swab.[IF COLLECT IN A SAME VIAL
INCREASES VIRAL YIELD]
NB:BEFORE COLLECTING SAMPLES PPE SHOULD BE
WEAR.

6. Case definitions {of swine flu[h1n1]}
 SUSPECTED CASE: A person with acute febrile illness with
onset within 7 days close contact with a person with confirmed
swine flu OR reside in a community/within 7 days of travel in
areas where ≥ 1 confirmed cases.
 PROBABLE CASE : A probable case of swine influenza A
(H1N1) virus infection is defined as a person with an acute
febrile respiratory illness who: is positive for influenza A,
but unsubtypable for H1 and H3 by influenza RT-PCR or
reagents used to detect seasonal influenza virus infection,
or is positive for influenza A by an influenza rapid test or
an influenza immunofluorescence assay (IFA) plus meets
criteria for a suspected case, or individual with a clinically
compatible illness who died of an unexplained acute
respiratory illness who is considered to be
epidemiologically linked to a probable or confirmed case.

7. Confirmed case: A confirmed case of swine influenza A (H1N1)
virus infection is defined as a person with an
acute febrile respiratory illness with laboratory
confirmed swine influenza A (H1N1) virus
infection at WHO approved laboratories by one or
more of the following tests:
 Real Time PCR
 Viral culture
 Four-fold rise in swine influenza A (H1N1) virus
specific neutralizing antibodies

10. Storage and transport of samples
 How to Store Specimens
 Store specimens at 4 °C before and during transportation within
48 hours
 Store specimens at -70 °C beyond 48 hours
 Do not store in standard freezer – keep on ice or in refrigerator
 Avoid freeze-thaw cycles
 Better to keep on ice for a week than to have repeat freeze and
thaw
 Transport:
 While transportation cold chain should be maintained.
 Follow local regulations on the transportation of infectious
material
 Coordinate with the laboratory .

11. Samples are send to NICED for
diagnosis.[in Kolkata]

12. CHOICEOF SAMPLE WITH CLINICAL COURSE

13. TESTS:

14. RAPID INFLUENZA DIAGNOSTIC TESTS
[RIDT]mechanism:

16. Algorithm to assist in the interpretation of RIDT
results during periods when influenza viruses are
circulating in the community

17. A test report[RT-PCR] from NICED

18. Advantages and Disadvantages of RIDTs
 Advantages:
 Produce quick result in 15 minutes or less, simple to perform
 Some RIDTs are approved for office/bedside use
 Disadvantages:
 Sub-optimal test sensitivity, false negative results are
common, especially when influenza activity is high
 Although specificity is high, false positive results can also
occur, especially during times when influenza activity is low
 Some RIDTs distinguish between influenza A or B virus
infection while others do not.

19. RT PCR

20. Reverse Transcription-Polymerase Chain Reaction (RT-
PCR)
 Advantages:
 Molecular assays are more sensitive and specific for detecting influenza
viruses than other influenza tests (e.g., rapid influenza diagnostic tests,
immunofluorescence, and viral culture)
 The likelihood of a false positive or false negative result is low and
therefore, the interpretation of the result is less impacted by the level of
influenza activity in the community
 Some, but not all molecular assays can distinguish between specific
influenza A virus subtypes
 Disadvantages:
 Results of RT-PCR and other molecular assays may not be available in a
clinically relevant time frame to inform clinical management decisions.
 RT-PCR generally not available for outpatient or emergency room
settings. For hospitalized patients, these assays are not always available
on-site.
 Respiratory specimens may need to be sent to a state public health
laboratory or commercial laboratory for RTPCR.
 Therefore, although the test can yield 3-8 hours, the actual time to
receive results may be substantially longer.
 RT-PCR and other molecular assays are generally more expensive .

22. Laboratory diagnosis of avian flu
 Samples
 Live bird
 Tracheal swab
 Cloacal swab
 Dead bird
 Organs
 Faeces of bird

23. Identification
 Procedures
 Inoculation of 9-11day old embryonated chicken
eggs followed by
 Haemagglutination immunodiffusion test
 Confirm presence of influenza virus
 Subtype determination with nonspecific antisera
 Strain virulence evaluation of
intravinouspathogencity index (IVPI) in 4-8 week
old chicken

24. Serology
 Tests available
 ELISA Detect antibodies to AI virus
 Doesn’t distinguish subtypes
 Agar gel diffusion
 Both within 1 week of infection
 haemagglutination inhibition test:
 Serotype specific test
 Available for each H subtype
 HI titres are positive a few days later than ELISA
DIAGNOSIS OF HUMAN AVIAN FLU SAME AS
OTHER INFLUENZA

27. ALWAYS MONITOR FOR FEATURES
OF COMPLICATIONS;
 Complications of influenza occur most frequently in patients
>64 years old and in those with certain disorders;
 including cardiac or pulmonary diseases, diabetes mellitus,
hemoglobinopathies, renal dysfunction, and
immunosuppression. neurospychiatric problems
 Pregnancy in the second or third trimester and postpartum
also predisposes to complications with influenza.
 Children <2 years old (especially infants)are also at high risk
for complications.
 People on long term aspirin therapy.
 Morbidly obese.

28. Supportive and treatment of
uncomplicated cases in hospital-
 Plenty of oral fluids, good nutritional support.
 Antibiotics for secondary infection. Suspected case not
having pneumonia do not require antibiotic therapy .
 Paracetamol or ibuprofen is prescribed for fever, myalgia and
headache. Aspirin is avoided for risk of Reye’s syndrome.
 For sore throat, short course of topical decongestants, saline
nasal drops, throat lozenges and steam inhalation may be
beneficial.
 Constantly monitored for clinical / radiological evidence of
LRTI.
 If the laboratory reports are negative, the patient would be
discharged after giving full course of oseltamivir

29. Antiviral medications
 Influenza antiviral medications should be started
as soon as possible after symptom onset
 These medications have not been shown to be
effective if administered more than 48 hours after
onset
 They can reduce illness severity and shorten
duration of illness
 They may also prevent serious influenza-related
complications (e.g., pneumonia or exacerbation of
chronic diseases)

30. Antiviral Drugs[mechanism]
Drug Virus Target
Amantadine /
Rimantadine (high
level of resistance
cases,not
recommended
now)
Influenza A strains Matrix protein /
haemagglutinin
Oseltamivir[oral],
Zanamivir[nasal]
PERAMIVIR[ IV
prep approved by
CDC in 2014]
Influenza strains A
and B
Neuraminidase
Inhibitor

32. Antiviral treatments:
Agents use recommd
for
C/I Adverse effect
Oseltamivir
(Tamiflu®)
treatme
nt
Any age no nausea, vomiting, serious skin reactions
and sporadic, transient
neuropsychiatric events (self injury
or delirium; mainly reported among
Japanese adolescents and
adults
chemop
roph
>3mont[if
needed
>14days]
Zanamivir
(Relenza®)
treatme
nt
7 yrs or
more
Copd
asthm
a,aller
gy.
bronchitis, cough,headache,dizziness,
and ear,
nose and throat Infections
Peramivir
(Rapivab®)
trtmnt 18yrs or
more
NA DIARRHEA, others as TAMIFLU
chemop
rophyls NA

33. Recommended dose and durations
Antiviral In children In adult
Oseltamivir
Treatmnt:5days
<1 yr-3 mg/kg/dose twice daily[ <3m-12mg;3-5m-
20mg:5m-25 mg BD
>1yr-15 kg or less, the dose is 30 mg BD
>15 to 23 kg, the dose is 45 mg BD
>23 to 40 kg, the dose is 60 mg BD
>40 kg, the dose is 75 mg BD
75mg BD
[DOSE
ADJUSTME
NT
NEEDED IN
RENAL
FAILURE
PATIENTS]
75mg OD
Prophylaxis:7days[moh
fw 10days}
If child is> 3 months <1yr old3 mg/kg/dose once
daily
If> 1 yr dose by child’s weight:
15 kg or less, the dose is 30 mg once a day
>15 to 23 kg, the dose is 45 mg once a day
>23 to 40 kg, the dose is 60 mg once a day
>40 kg, the dose is 75 mg once a day
Zanamivir(Relenza®)
TREATMENT 5DAYS
10 mg (two 5mg inhalations) twice daily(FDA
approved and recommended>7 yrs
SAME
Prophylaxis 7days
10 mg once for>5yrs
Peramivir;for treatmnt
(Rapivab®)
N/A IN CHILD; IN >18YRS.600 mg IV SINGLE
DOSE ONLY ONCE.

34. Pharmacological treatment and prophylaxis of
avian flu[WHO]
 Some evidence suggests that some antiviral drugs,
notably oseltamivir, can reduce the duration of viral
replication and improve prospects of survival.
 Dose and duration of the drug for treatment is same as
above.
 Chemoprophylaxis: for 7-10 days of last known exposure
 No recommendation of prophylaxis in children below one
year.
 Chemoprophylaxis is given to high and moderate risk
individuals who are close contacts with the case,
professionals handling the patients and persons who are
having contact with infected materials.

36. Management of complicated influenza
 Maintain airway, breathing and circulation (ABC)
 IV Fluids.
 Parentral nutrition.
 Oxygen therapy-Patients with signs of tachypnea, dyspnea,
respiratory distress and oxygen saturation less than 90 per cent
should be supplemented with oxygen therapy
 ventilatory support- Patients with severe pneumonia and
acute respiratory failure (SpO2 < 90% and PaO2 <60 mmHg with
oxygen therapy) must be supported with mechanical ventilation.
 Invasive ventilation is preferred. To reduce spread of infectious
aerosols, use of HEPA filters on expiratory ports of the ventilator
circuit / high flow oxygen masks is recommended.
 Antibiotics for secondary infection.
 Patient on mechanical ventilation should be administered
antibiotics prophylactically to prevent hospital associated
infections .
 Vasopressors for shock.

37. Management cont.
 Immunomodulating drugs has not been found to be
beneficial in treatment of ARDS or sepsis associated multi
organ failure. High dose corticosteroids in particular have no
evidence of benefit and there is potential for harm.
 Low dose corticosteroids (Hydrocortisone 200-400 mg/
day) may be useful in persisting septic shock (SBP < 90).
 For patients who continue to be symptomatic even after 10
days of treatment or those cases with respiratory distress and
in whom secondary infection is taken care of, and if patient
continue to shed virus, then resistance of the patients to anti
viral would be tested. The dose of anti viral may be adjusted
on case to case basis.

38. Complications of avian flu is very fatal;
people often die with multi organ failure

39. Discharge criteria:
 It has been observed that some of the patients even though
asymptomatic, continue to test positive for influenza A
H1N1. A treated and recovered patient, even though testing
positive, has very little possibility of infecting others ;
 Patients who responded to treatment after two to three
days and become totally asymptomatic should be
discharged after 5 days of treatment. There is no need for a
repeat test.
 Patients who continue to have symptoms of fever, sore
throat etc. even on the 5th day should continue treatment
for 5 more days. If the patient become asymptomatic
during the course of treatment there is no need to test
further.

42. Chemoprophylaxis
 (i) Chemoprophylaxis for health care workers at high risk: The
treating physicians and other paramedical personnel at the isolation
facility would be put on chemoprophylaxis.
 (ii) Chemoprophylaxis for contacts :Chemoprophylaxis is advised for
those contacts with high risk (with under lying systemic diseases;
extremes of age[< 5 years and 65> years]
 In phase-5, if the clusters are reported for the first time, and given that
those exposed are known and can be traced easily, then family, social
and community contacts should be given Chemoprophylaxis.
 (iii) Mass Chemoprophylaxis: The strategy of containment by
geographic approach by giving oseltamivir to every individual in a
prescribed geographic limit of 5 km from the epicenter(The village/city
where the cluster is reported) would be applied:
 1. If the virus is lethal and causing severe morbidity and high mortality
 2. If the cluster is limited by natural geographic boundaries.
 This decision by State Health Department/MOHFW.
 All close contacts of suspected, probable and confirmed cases. Close
contacts include household /social contacts, family members, workplace
or school contacts, fellow travellers etc.
 All health care personnel coming in contact with suspected, probable or
confirmed cases

43. Influenza Vaccine,
who should receive it[HIGH RISK
GROUPS]  Persons 65 yrs or older
 Persons with heart,
pulmonary, renal and
metabolic diseases.
 Persons in nursing
homes and other long-
term care facilities
 Persons 6 mos-18 yrs
old receiving aspirin
therapy

44. Influenza vaccine recipients--
continued
 Women in 2nd or 3rd
trimester of pregnancy
during flu season.
 Household members of
persons in high-risk
groups
 Health care workers
and others providing
essential community
services.

45. Vaccination for Children
 Children under 6 months old are the paediatric group at
highest risk of influenza complications, but they are too
young to get an influenza vaccine. The best way to protect
young children is to make sure members of their household
and their caregivers are vaccinated.
 Influenza vaccination is recommended for all children 6
months of age and older every year.
 Primarily two doses required at least four weeks apart for
upto 8 years.
 9 year onward single dose is recommended.

46. Avian influenza vaccine for birds
 Convential vaccine
 Inactivated oil emulsion vaccine used world wide
 Recominant vaccine
 Vector I LT vaccine or pox
 Heteroglogous vaccine
 In avian influenza contain the same agglutinin
 A different Neuraminidase
 THERE IS NO AVAILBLE VACCINE FOR HUMAN
AGAINST AVIAN FLU.

47. STORAGE AND STABILITY
Store at 2° to 8°C (35° to 46°F). Do not freeze. Discard
product if exposed to freezing.
Protect from light. Do not use vaccine after expiration date

48. When should vaccination occur?
 Flu vaccination should begin soon after vaccine
becomes available, ideally by October. However, as long
as flu viruses are circulating, vaccination should
continue to be offered throughout the flu season, even
in January or later.
 While seasonal influenza outbreaks can happen as early
as October, most of the time influenza activity peaks in
January or later. Since it takes about two weeks after
vaccination for antibodies to develop in the body that
protect against influenza virus infection, it is best that
people get vaccinated so they are protected before
influenza begins in the community.

49. Vaccine Recommendations
• Ideally, all
individuals
should have the
opportunity to be
vaccinated
against
influenza.
• Priority should
be given to high
risk population
• All those
aged over 6
months in a
clinical at-
risk group
• Only in all
high risk
children >6
months
• Universal
Vaccination
of all
children from
the age of 6
months.
• Special
attention for
children upto
60 months
• Routine
influenza
vaccination is
recommended
for all persons
aged ≥6 months
*CEVAG: Central European Advisory Group
http://www.who.int/docstore/wer/pdf/2002/wer7728.pdf
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr59e0729a1.htm?s_cid=rr59e0729a1_e
http://www.sehd.scot.nhs.uk/cmo/CMO(2010)14.pdf
http://www.biomedcentral.com/content/pdf/1471-2334-10-168.pdf
*

50.  WHO determines influenza vaccine contents
annually
 Typically, 3 live attenuated virus strains, which
antigenically represent the influenza strains likely to
circulate the next flu season, are included in the
formulation each year .
 Production of new vaccine is often difficult due to
frequent changes of strains due to drifting/shifting

51. Mechanism of influenza vaccine

54. INTERNATIONAL SURVEILLANCE NETWORK
VACCINE MANUFACTURER
M A M J J A S O N D J FF M
Process of Influenza Recommendations and
Vaccine Availability
WHO
(Northern hemisphere)
PRODUCTION
WHO
(Southern hemisphere)
PRODUCTION
Chalumeau HP. Vaccine manufacture at the time of a pandemic influenza. European journal of epidemiology
1994;10: 487-490

55. Influenza Vaccine Composition for the 2014–15 Season [ACIP ]
 Trivalent influenza vaccines contain-hemagglutinin (HA)
derived from an A/California/7/2009 (H1N1)like virus, an
A/Texas/50/2012 (H3N2)like virus and a
B/Massachusetts/2/2012like(Yamagata lineage) virus.
 Quadrivalent influenza vaccines will contain these antigens,
and also a B/Brisbane/60/2008like(Victoria lineage) virus.
 Both LAIV and IIV have been demonstrated to be effective in
children and adults. In adults, most comparative studies have
demonstrated either similar efficacy or that IIV was more
efficacious. However, several studies have demonstrated
superior efficacy of LAIV in children.
 Recombinant IV prepared from purified HA protiens of first 3
viruses.
 Influenza vaccination should not be delayed to procure a
specific vaccine preparation if an appropriate one is already
available.

56. ‘Made in India’ H1N1 vaccine
 Swine flu vaccine in India was launched
by Health department
 Given by I/M or intranasal route.
 Vaccines manufactured by
 Zydus Cadila
 Serum institute of india
 Panacea biotech
 Bharat biotech

57. Vaccine available in INDIA
Brand names manufacturer combinations type
VAXIGRIP Sanofi Pasteur Influenza [A&B]
swine flu
IIV[split
virion]trival /inj
INFLUVAC Solvay Pharma India Pvt
Ltd
same same
INFLUGEN Lupin Laboratories Ltd. Same same
FLUARIX Glaxo Smithkline
Pharmaceuticals
same same
NASOVAC Serum Institute of India
Ltd
same same
AGRIPAL Chiron Panacea same same
VaxiFlu S Zydus Cadila Health Care
Ltd.
same same
NASOVAC-S Serum Institute of India
Ltd
Same[USED>2 YRS] LAIV[trivalent]
Intranasal spray

58.  Active Ingredients:
 VAXIGRIP have been prepared on eggs and are made
from inactivated parts of the
 following Influenza virus strains:
 A/California/7/2009 NYMC X-
179A(A/California/7/2009 [H1N1]pdm09 - like),
 A/Texas/50/2012 NYMC X-223A (A/Texas/50/2012
[H3N2] – like)
 B/Massachusetts/2/2012 NYMC BX-51B
(B/Massachusetts/2/2012-like)

59. Nasovac-S
 Live, attenuated, trivalent seasonal influenza
vaccine for administration by intranasal spray
 Supplied along with sterile water for inhalation as a
diluent, syringe, needle, intranasal spray device and
dose divider.
 Each vial of the vaccine contains following strains:

61. Advantages of LAIV
Ref: MMWR Morb Mortal Wkly Rep. 2014 Aug 15;63(32):691-7.
Adv.
Serum
antibodies
Nasal
Specific
intranasal
IgA
Cell
mediated
immune
responseProtection
against
drifted
virus
Mimic
natural
route of inf
Painless
Herd
immunity

62. Head to Head comparison of LAIV & IIV
LAIV IIV
Grows in nasopharaynx Not grow
Nasal spray Injection
Grows in cooler areas of nasal tract but
stop growing in LRTI
Not grow
Mimic natural infection and induce
double layer immunity
Serves only as a dose of antigen to the
immune system
Induce local, systemic and cell mediated
immunity
May not induce local immunity, good
systemic response
Provide local immunity No local immunity
More effective Effectiveness less than LAIV
Painless Painful
Negligible side effect Reported side effects
Cost effective Comparatively expensive
Provide herd immunity Not possible
Preferred in children Children afraid of needles

63. Contraindications and precautions
IIV3/4:C/I- Severe allergic reaction to any component of the vaccine,
including egg protein, or after previous dose of vaccine.
Precautions: Moderate to severe illness with or without fever; history
of GB syndrome within 6 weeks of receipt of influenza vaccine.
LAIV:C/I- severe allergic reactions as above and
 Concomitant use of aspirin or aspirin containing medications in children
and adolescents.
 In addition, ACIP recommends LAIV4 not be used for pregnant women,
immunosuppressed persons, persons with egg allergy, and children aged
2–4 years who have asthma or who have had a wheezing episode noted in
the medical record within the past 12 month.
 LAIV should not be administered to persons who have taken influenza
antiviral medications within the previous 48 hours.
 Persons who care for severely immunosuppressed persons who require a
protective environment should not receive LAIV, or should avoid contact
with such persons for 7 days after receipt.
 Precautions: As of IIV and
 Asthma in persons aged 5 years and older.
 Medical conditions which might predispose to higher risk for
complications attributable to influenza

64. Side effects:
 Mild side effects usually begin soon after you get the
vaccine and last one to two days.
Possible mild side effects of the flu shot include:
 Soreness, redness, and swelling at the injection site
 Fainting, mainly in adolescents
 Headaches
 Fever
 Nausea
Possible mild side effects of the nasal spray include:
 Runny nose
 Wheezing
 Headache
 Vomiting
 Muscle aches
 Fever

65. Serious side effects:
Serious side effects usually begin within a few
minutes to a few hours after receiving the shot.
Possible serious side effects of vaccination
include:
 Difficulty breathing
 Hoarseness
 Swelling around the eyes or lips
 Hives
 Paleness
 Weakness
 Racing heart
 Dizziness
 Behaviour changes
 High fever

66. Influenza vaccine dosing algorithm for children aged 6
months through 8yrs[ACIP] for 2014-15

67. Recommendations regarding influenza vaccination of
persons who report allergy to eggs [ACIP]

69. Indian Scenario:Reality
 Limited data in public domain on annual Influenza cases
and deaths in Indian scenario
 Influenza vaccine is in Indian market since 2004
 There is not much of published data on safety, tolerability
and effectiveness of Influenza vaccine in Indian children
70
*India to compile database for influenza. Available from: URL:
http://www.livemint.com/2009/05/31215156/India-to-compile-database-on-s.html. Accessed on 22 May, 2010.
**Joseph L Mathew. Influenza vaccination for children in India. Indian Pediatrics. 2009 ;46:304-307.