Influenza is caused by RNA viruses of three types - A, B, and C. Type A is the most virulent and causes pandemics through antigenic shifts. It has various subtypes like H1N1, H5N1, H3N2. Type B causes epidemics. Type C causes mild illness. Influenza spreads during winters through droplets. It can cause complications like pneumonia. Diagnosis involves virus isolation, antigen detection and serology. Vaccination and antiviral drugs like oseltamivir are used for prevention and treatment. The 2009 H1N1 virus caused a pandemic and is now a seasonal variant.
2. Introduction
1. Influenza viruses cause the most virulent
respiratory tract infections in humans
2. common cause of zoonotic infections.
3. Notorious for changing antigenicity and
increasing mortality
3.
4. Types
1. Three types (genera) of influenza viruses
affecting humans: A, B, C.
2. All three are antigenically distinct and no cross
immunity.
3. A virus : Has been the cause of all known
pandemics till date. Has antigenic variations
and subtypes
4. Influenza type C: mild respiratory illness and
are not thought to cause epidemics.
5. Problem statement
1. Truly global disease.
2. Pandemics occur every 10-40 years due to
antigenic shift.
3. 1918- Spanish influenza
4. 1968- Hong Kong influenza.
6. Problem statement (cont)
1. Epidemics:
1. sudden onset and rapid spread
2. Due to animal reservoirs and human carriers
3. Inf. A- Every 2-3 years
4. Inf.B- Every 4-7 years
2. Sporadic cases also can occur
9. Agent factors- Antigenicity
1. Large, single-stranded RNA virus.
2. Family Orthomyxoviridae.
3. 3 types A,B & C
4. Influenza A viruses are divided into subtypes based on two proteins on
the surface of the virus:
1. the hemagglutinin (HA): helps attachment of virus to cell.
2. the neuraminidase (NA): release virus into cells.
5. 18 different hemagglutinin subtypes (H1 to H18).
6. 11 different neuraminidase subtypes (N1 to N11).
7. Only H1, H2, H3 and N1, N2 are found in humans
10.
11. Present circulating viruses
1. Inf. A (H5N1) – since 1997 of avian influenza from Hong
Kong
2. Inf. A (H1N1) – since 2009 of swine influenza from Mexico
3. Inf. A (H7N9)- caused an outbreak in China in 2013 and
second larger outbreak in 2014
4. Inf. A (H3N2v) virus caused human infections in USA from
2011-2013.
5. Type B virus: no antigenic shifts; no subtypes; causes
epidemics throughout the world
6. virus type C is a sporadic cause of predominantly mild
upper respiratory tract illness. No subtypes
12. Antigenic changes
Antigenic shift:
1. It refers to abrupt change due to reassortment of viral
gene segments when there is simultaneous infection by
more than 1 strain of influenza in a single human or
animal host, resulting in emergence of virulent subtypes.
2. This occurs more in influenza A viruses, which have
multiple avian and mammalian hosts acting.
Antigenic drift:
1. It refers to point mutation in viral genes during
replications & repeatedly over a period of time and
becomes a distinct strain.
13.
14. Significance
• Owing to the above mentioned processes of
genetic reassortment the antigenic
determinants present on the viral surface
changes thereby reducing our immune
systems ability to identify and eliminate the
pathogen.
• This leads to pandemics and increased
mortality
15. Reservoir of infection
• The major reservoir is animals.
• It is believed that the recombination of human
and animal viral strains are responsible for
emergence of new strains.
16. Source of infection
• Infected human Case
• Subclinical case
• The respiratory secretion (droplet infection)
• The period of infectivity is 1-2 days before and
after the onset of symptoms.
17. Host factors
• Age- high risk include children below 18
months
• old people above 65 years
• the immunocompromised
• Sex equal
• Human mobility
• Immunity- antibodies appear by 7 days, max
level by 2 weeks, revert to normal by 8-12
months.
20. Pathogenesis and clinical features
1. Virus enters respiratory tract Inflammatio
and necrosis of superficial mucosa
Secondary bacterial infection feve, chills,
respiratory distress pneumonia
2. No viremia
21. Complications
1. Acute sinusitis
2. Otitis media
3. Purulent bronchitis
4. Pneumonia- suspect if fever persists >5 days or recurs
after convalescence.
5. Reye syndrome- fatty liver with encephalopathy (30%
mortality) A rare complication associated with
1. type B virus
2. Aspirin use
3. Young children
22. Lab Diagnosis
1. Viral isolation from nasopharyx.
2. IFA technique for detection.
3. Egg inoculation for isolation
4. Serology: Hemagglutination inhibition
5. Paired serology: Requires both acute and
convalescent sera. Four fold increase in titer
considered significant.
6. Most sensitive is ELISA.
23. Prevention
• General measures
– Good ventilation.
– Avoiding crowded places during epidemics.
– Covering face while coughing
• Immunisation
– Should contain both H and N components ( 70 to 90
% efficacy)
– Limitation: Has to be given atleast 2-3 weeks before
epidemic to be effective. Epidemics are
unpredictable.
24. Prevention(Cont)
• Immunisation recommended for:
– Those with chronic debilitating illness and their
caretakers.
– Public servants during emergencies.
– HIV patients
• Influenza vaccines: Killed vaccines:
– Chick embryo derived vaccine
– Killed by formalin or beta propionolactone
– Standardised as per HA content
25. – Reconstituted using saline
– One dose contains 15 microgms of HA
– Route : SC or IM
– Dose : single dose of 0.5 ml for adults and children
>3 yrs and 0.25 ml for children 6-36 months.
– If unprimed and 2 doses 3-4 weeks apart
recommended.
– Protective value 70-90 percent
– Lasts for 6-12 months
– Revaccinate every year.
• S/E Fever, local inflammation and rarely
guillian-barre syndrome.
26. • Live vaccines:
– Trivalent
– Single dose
– Route: intranasal spray
– Recommended for 2 to 49 years.
– Avoid if individual to be immunized is in close
contact with immunocompromised individuals.
27. • Contraindications to vaccines:
– Allergy to chicken egg
– H/O Anaphylaxis to vaccine or its constituents
– Who have developed GBS within 6 weeks of
vaccination.
– Children <6 months
– Acute illness with fever wait for it to subside.
28. Antiviral drugs
• Neuraminidase inhibitors:
– Used for type A and B
– Both for prohylaxis and treatment
– Oseltamivir 75 mg/ day for prophylaxis
75 mg bd for 5 days for therapy.
– Zanamavir 10 mg inhalational twice daily for
therapy and once for prophylaxis.
• Inf A – Zanamavir Unitherapy
–Oseltamavir and rimantidine combination.
• Inf B: Either zanamavir or oseltamivir.
29. Avian influenza
• Predominantly affects birds.
• H5N1 considered to have pandemic potential
and is being closely monitored.
• Inter species transmission fortunately is not
easy for the species as of this moment.
30. H1N1- Pandemic influenza (2009)
• Immunologically new strain capable of
affecting lower respiratory tract and causing
rapidly progressive pneumonia.
• H1N1 pandemic declared on 11th June 2009.
• Now in post pandemic phase
• In india 937 cases reported , 218 dead a CFR
of 23.2% during 2014.
• Expected to continue as a seasonal variant.
31. Defintions in H1N1
• Suspected case: person with acute febrile illness (>380 C)
with onset
1.within 7 days of close contact with confirmed case (or)
2.within 7 days of travel to an area with confirmed case (or)
3. resides in a community with one or more confirmed case.
• Probable case: person with acute febrile respiratory
illness-
1. positive for influenza A but untypable for H1 and H3 by RT-
PCR (or)
2. positive for H1N1 by rapid test or IFA and meets criteria for
suspected case (or)
3. individual with a clinically compatible illness who died of
unexplained acute respiratory infection who is
epidemiologically linked to a confirmed case.
32. • Confirmed case: person with acute febrile
respiratory illness with laboratory confirmed
Influenza A by one of the following WHO
approved method:
– RTPCR
– Viral culture
– Four fold increase in H1N1 virus specific
neutralizing antibodies.
33. Lab diagnosis of H1N1
• RT PCR best and most sensitive.
• Specimen : nasal / nasopharyngeal.
– If patient presents with LRI then tracheal and
bronchial aspirates will have higher yield.
• Diagnostic confirmation should in no way
deter antiviral therapy if a diagnosis of H1N1
is made clinically and epidemiologically.
34. Infection control
1. Use particulate respirator during sample
collection (N 95 or FFP2) and other protective
gear.
2. Isolation of suspected case for 7 days after the
onset of illness or 24 hours after the resolution
of fever whichever is longer.
3. Immunocompromised patients shed virus for
longer time.
35. H1N1 Vaccine
• Inactivated vaccine:
– Monovalent
– Derived from california/7/2009(H1N1)like strain.
– 0.5ml IM
– Thiomersal added to prevent bacterial
cotamination.
– Use on same day as opening vial.
– Stored at 2-8 degree.
– Becomes effective 14 days post vaccination.
36. Live vaccine
• Intranasal
• Health care workers are first priority.
• Other target groups inorder of priority:
– Pregnant women
– >6month with severe chronic illness
– Healthy adult 15-49 years
– Healthy children
– Healthy adult 49-65 years
– Healthy adult >65 years
37. Treatment of H1N1
• Susceptible to NAI but resistant to M2
Inhibitors.
• Hence oseltamivir and Zanamavir are used.
• Rimantidine and amantdine are avoided.
• Chemoprophylaxis is by oseltamivir 10 days
after the last exposure.
