Dr. Jagadish Nuchin MD,MBA

April 8, 2023 1

Problem statement - In pigsSwine flu or pig flu or hog flu or SIVEndemic (H1N1 and H3N2) in most

of the countries- worldwide- OIE 25 percent of animals show

antibody evidence of infection. (51% in north-central America)

Occurs all the monthsOutbreaks usually occur in cold

seasonH1N1 strains are circulating in pig

population since 1930 and H3N2 since 1998

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Transmission of swine influenza virus from pigs to humans is not common

( Zoonotic swine flu)- very rare

So far only few such cases have been occurred globally with no man to man transmission (WHO)

Pigs have been described as ‘mixing vessels’ for the various influenza virus strains-OIEApril 8, 2023 3

Problem statement in ManInfluenza is an ARTI caused by

influenza virusesOccurs in all the countries affecting

5-15% of the global population, resulting in severe illness in 3-5 million patients and causing 250,000-500,000 deaths worldwide.

In addition to these annual epidemics, the influenza A virus has caused three major global pandemics during the 20th century: the Spanish flu in 1918, Asian flu in 1957 and Hong Kong flu in 1968-69.April 8, 2023 4

Year Deaths(Millions)

CFR Influenza A subtype

PSI

Asiatic

( Russian) flu

1889–1890 1 NA Possibly H2N2 ?

Spanish flu

1918 20-1002.5

H1N1 5

Asian flu 1957 2 0.1 H2N2 2

Hong Kong

1968 1 0.1 H3N2 2

Epidemiological features

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It may occur in several forms- as Subclinical cases – being manifest only by

serological surveys (1/3 of the total) Pandemics- every 10-15 years once (due to

major antigenic changes) Epidemics –tend to occur at intervals of 2-3

years in case of Influenza A and 4-7 years in case of Influenza B. this periodicity is not regular like measles and diphtheria

Endemics – in most of the countries

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Unique features of influenza epidemicsEpidemic starts in a characteristic way.Begins with a few cases, soon followed by

sudden outburst of disease - indicated by rise in the incidence of febrile respiratory illness

in children and old- high attack rates-10-50% Increased hospitalization of cases Sickness-absenteeism in schools/working place

Epidemic reaches its peak in 3-4 weeks then tends to decline

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Factors contributing to easy and fast spread of the diseaseShort incubation periodLarge number of mild and subclinical cases

High proportion of susceptible population

Short duration of immunityAbsence of cross-immunity (sub-type specific)

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Influenza virusesThey are RNA virusesInfect mammals and birds and cause ARTIThe name influenza comes from the

Italian influenza, meaning "influence" (Latin: influentia).

The word influenza was first used in English in 1743

Virus was first discovered in pigs by Richard Shope in 1931.

Virus was isolated in Humans in 1933.April 8, 2023 10

MorphologyInfluenza viruses have a very similar

structure.The core consists of RNAThe influenza viruses are classified

into A,B, and C serotypes based on type of RNA (M1 and NP internal antigens)

The envelope has an inner protein layer and an outer lipid layer

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Influenza virusesBelong to Orthomyxoviridae family, which

comprises five genera:1.Influenza virus A –Birds (mainly wild aquatic

birds) and mammals2.Influenza virus B – exclusively humans and

rarely seals3.Influenza virus C – man and pigs4.Isa virus -infect salmon5.Thogoto virus-infect vertebrates and

invertebrates, such as mosquitoes and sea lice.

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Two types of spikes (peplomers) are projected from the

envelope – Haemagllutinin ( more in number) and Neuraminidase (less in number)

The virus particle is 80–120 nanometres in size

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Influenza virus A

• Wild aquatic birds are the natural hosts for a large variety of influenza A.

• Occasionally, viruses are transmitted to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics

• Most virulent and cause the most severe disease.

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Influenzavirus B• Influenza B almost exclusively infects

humans and seals• Is less common than influenza A. • Mutation takes place very slowly (less

genetically diverse), with only one influenza B serotype.

• immunity to influenza B is usually acquired at an early age.

• However, influenza B mutates enough that lasting immunity is not possible.

• pandemics are less likelyApril 8, 2023 15

Influenzavirus CInfects humans and pigs and can cause severe illness and local epidemics.

However, influenza C is less common than the other types and usually seems to cause mild disease in children.

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Influenza A H1N1

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Classification of Influenza AInfluenza A viruses are further classified,

based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N).

Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans (CDC)

Influenza A virus strains are assigned an H number and an N number based on, which forms of these two proteins, the strain contains.

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The Influenza A genome encodes 11 proteins: hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), M1, M2, NS1, NS2(NEP), PA, PB1, PB1-F2 and PB2.

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• HA and NA are large glycoproteins on the outside of the viral particles.

• HA is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles.

• Thus, these proteins are targets for antiviral drugs.

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The Influenza A serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:• H1N1, which caused Spanish flu in 1918 and has been identified as

the serotype of the 2009 outbreak of swine flu originating from Mexico

• H2N2, which caused Asian Flu in 1957 • H3N2, which caused Hong Kong Flu in 1968 • H5N1, a pandemic threat in the 2007–08 flu season • H7N7, which has unusual zoonotic potential • H1N2, endemic in humans and pigs • H9N2 • H7N2 • H7N3 • H10N7

• In 2009, a recombinant influenza virus derived in part from H1N1 was first detected in Mexico and the United States.

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New Strain- Influenza A (H1N1)Origin-not known. But researchers say

that the new H1N1 strain first evolved around September 2008 and circulated in the human population for several months before the first cases were detected.

First confirmed case- April 13th 2009 ( Women died of pneumonia) in Oaxaca, Mexico.

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ReassortmentThe mixing of the genetic material of two

similar viruses infecting the same cell. In particular, reassortment occurs among

influenza viruses, whose genomes consist of eight distinct segments of RNA.

These segments act like mini-chromosomes, and each time a flu virus is assembled, it requires one copy of each segment.

The new reassortant strain will share properties of both of its parental lineages.

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Reassortment

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H1N1

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The Influenza A H1N1 virus contains the gene segments from 4 viruses

North American swineNorth American AvianNorth American human Eurasian swine

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As on today8 June 2009 -- As of 06:00 GMT, 8 June 2009,

73 countries have officially reported 25,288 cases of influenza A(H1N1) infection, including 139 deaths.

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India as on 8th June

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1) Phase 1- no influenza viruses circulating among animals have been reported to cause infections in humans.

2) Phase II- an animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat.

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3) Phase III-an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks.

4) Phase IV- human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.”

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5) Phase V-human-to-human spread of the virus into at least two countries in one WHO region.

6) Phase VI- community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.

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Why concernA novel strainMan to man transmissionVirulenceNo natural or artificial immunity

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Source of infection- A case or a subclinical case

Period of infectivity- the virus is present in the nasopharynx from 1-2 days before to 3-7 days after the onset of symptoms

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ImmunityAll the three are antigenically unrelated,

hence no cross protection and it is subtype-specific

Antibodies appear 5 days after infection reach the peak in 2 weeks. After 8-12 months, the titre drops to preinfection level

Antibodies against HA- neutralizes the virus ( inhibits initiation of infection)Antibodies against NA-reduces the disease

severity and decreases the ability to transmit

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Antibodies against ribonucleoprotein are type specific- useful in typing viral isolates as A or B.

Serum antibodies persist for many months whereas secretory (IgA) antibodies in nasal secretions are short lived.

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Seasonepidemics usually occur in winter months in Northern hemisphere and in winter or rainy season in the Southern hemisphere. In India, epidemics often occurred in summer

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Mode of transmissionBy three ways- 1) by direct transmission- when an infected

person sneezes mucous into eys, nose or mouth.

2) by aerosols produced by infected people coughing, sneezing and spitting and

3) through hand-to-mouth transmission from either contaminated surfaces (Fomites) or direct personal contact, such as a hand-shake.

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Influenza can also be transmitted by contact with infected bird droppings (in case of avian influenza), saliva, nasal secretions, feces, blood and with contaminated surfaces.

Airborne aerosols have been thought to cause most infections, although which means of transmission is most important is not absolutely clear.

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Survival of virus Influenza viruses can be inactivated by sunlight,

disinfectants and detergents 1) Hard non-porous surface-

-Transferable to hands up to 24 hrs - recoverable for >24 hrs2) Cloth and paper- Transferable to hands up to 15 minutes recoverable for 8-12 hrs3) On hands- viable up to 5minutes only at high viral titre Required humidity is 35-40% and temperature 28

degree CelsiusApril 8, 2023 43

Overcrowding enhances the transmission

Portal of entry- RTIncubation period- 18-72 hrs ( up to 7 days-WHO)

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Pathogenesis The virus enters the RT, causes inflammation

and necrosis of superficial epithelium of tracheal and bronchial mucosa, followed by secondary infection.

There is no vireamia

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Clinical symptoms are similar to seasonal influenza -chills, fever, running nose, sore throat, muscle pains, severe headache, coughing, weakness, general discomfort, shortness of breath and difficulty in breathing

April 8, 2023 46

Risk group/factorsRisk group (associated with more serious disease

and increased mortality from influenza- complications are more like pneumonia, bronchitis, sinus, and ear infections)

Young childrenWeakOldWith chronic pulmonary diseasesSmoking

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Contrast to seasonal flu, here the symptoms are severe, last longer and complications are common with high mortality

The most dreaded complication is pneumonia ( especially in children and old), which should be suspected if fever persists beyond 4-5 days or recurs abruptly after convalescence.

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Laboratory diagnosis 1) Virus isolation- Specimen- Nasopharyngeal

secretions are the best specimens as they contain the large amounts of virus-infected cells. Egg inoculation of virus may be required

Real time RT PCR The virus can also be detected by Fluorescent antibody technique

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2) Paired Sera-

First sample- in acute phase, not later than 5th day

Second sample- in convalescent phase- 10-15 days after the onset of disease

Fourfold rise- DiagnosticAt least 2-5ml of serum should be sent

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Where to send in India1. NIV Pune2. NICD new Delhi3. Govt. of India, Influenza centre, Pasteur

institute, Coonoor.4. Haffkine Institute, Mumbai5. School of Tropical Medicine, Kolkata6. AIIMS, New Delhi7. Armed Forces Medical College, Pune

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Case definitions Suspect Case Defined as an individual with an acute febrile respiratory illness (fever >38°C) with onset of symptoms:– Within 7 days of travel to affected areas; or– Within 7 days of close contact with a

confirmed or probable case of Swine Influenza A (H1N1)

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Probable Case

Defined as an individual with an acute febrile respiratory illness (fever >38°C) with an

influenza test that is positive for Influenza A but is un-subtypeable by reagents used to detect seasonal influenza virus infection, OR;

an individual with a clinically compatible illness or who died of an unexplained acute respiratory illness who is considered to be epidemiologically linked to a probable or a confirmed case.

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Confirmed Case

Defined as an individual with laboratory confirmed Swine Influenza A (H1N1) virus infection by one or more of the following tests:

Real-time RT-PCR; Viral culture; Four-fold rise in Swine Influenza A (H1N1)

virusspecific neutralizing antibodies

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Treatment- oseltamivir and zanmivir

Oseltamivir- both for treatment and prophylaxis

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Infants Dosage Duration

<3 months 12 mg BD 5 days

3-5 months 20mg BD 5 days

6-11 months 25mg BD 5 days

Others

<15kg 30mg BD 5 days

15-23kg 45mgBD 5 days

24-40kg 60mgBD 5 days

>40kg 75mg BD 5 days

Dose and duration can be modified as per clinical condition.

Also available as syrup (12mg/ml)

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Prevention and Control

Less successful

During the outbreak-

Use of masks- in cases and contacts

Use of hand kerchief while sneezing/coughing

If you don't have a tissue, cough or sneeze into your sleeve.

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Hand washing with disinfectants

Avoid touching mouth, nose or eyes with hands unless you wash your hands.

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Avoid overcrowdingGood ventilation of buildingStay at home at the first sign of

influenzaNo travelling to affected countries/areasScreening at air/sea port

No risk of flu transmission from consumption of pork

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Vaccines Right now no vaccines for this new strainWHO/CDC assured a vaccine in another 6-8

months now

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Bottlenecks for vaccinationInfluenza epidemics are unpredictableBecause of antigenic variation, new vaccines

are constantly required- A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and different strains become dominant.

Right now no vaccine for current strain, may take several months for manufacturing huge quantity(CDC)

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Thank you all

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