SWINE FLU

Dr.vijay

VIROLOGY OF INFLUENZA Spherical

Enveloped ,

Segmented

Negative Sense

8 SINGLE Straded

RNA Virus

TAXONOMY

Anitgenic Drift

Mutation That Take Place Within The Genome

Causes Changes In Hemagglutinin And Neuraminidase Of Influenza Virus Due To Point Mutations

This Involves No Change In Serotype; There Is Merely An Alteration In Amino Acid Sequence Of HA Or NA Leading To Change In Antigenicity.

Drift Variants Can Cause Epidemics And Lasts For 2 To 5 Years, Before Being Replaced By A Different Strain.

ANTIGENIC SHIFTRe-assortment (mixing of genetic

meterial ) among the genetic materials of subtypes resulting in A new virus.

Involves major antigenic changes in which a new HA or NA subtype is introduced into the human population.

Caused by reassortment, typically between human , avian and swine strains.• Double reassortment• Triple reassortment.(2009-

swineflu(H1N1))§ Antigenic shift may result in a new virus

easily transmissible from man to man for which the population has no immunity :

results in pandemics

.

PATHOGENESIS

PATHOGENESIS

High affinity for the tracheal cells with sialic acid receptors. HA ataches to Sialic acid receptors. Preferentially binds to the N-acetylneuraminic acid attatched to the penultimate glucose sugar

by α 2,6 linkage. (2,3 linkage for avian flu)

the virus multiplies in bronchial epithelium within 16 hr of infection and causes

focal necrosis of the bronchial epithelium,

focal atelectasis, and gross hyperemia of the lungs.

Epithelial cell damage

Airway plugging

Peribronchial and perivascular mononuclear infiltrates.

TRANSMISSION Short incubation period, usually 1-4 days. Source of infection -Case or sub-clinical case Reservoir of Infection - Human Spread by respiratory droplets

Person to person,Direct contact, rare aerosol

Highly contagiousINFECTIOUS PERIOD:

üAdults: 1 day prior to symptoms & 5 days post illness startsüChildren: >10 daysü Immune compromised shed virus for weeks to months

Virus is detectable just before symptom onset.Usually not detectable after 5-10 daysPeople with flu can spread it to others up to about 6 feet away

SWINE FLU SYMPTOMSSWINE FLU is a contagious respiratory illness caused

by flu viruses. It can cause mild to severe illness, and at times can lead to death. The flu is different from a cold. The flu usually comes on suddenly. People who have the flu often feel some or all of these symptoms:

Fever* or feeling feverish/chills

Cough

Sore throat

Runny or stuffy nose

Muscle or body aches

Headaches

Fatigue (tiredness)

Some people may have vomiting and diarrhea, though this is more common in children than adults.

* It's important to note that not everyone with flu will have a fever.

Symptoms

Symptoms Number (n=268) %

Fever 249 93%

Cough 223 83%

Shortness of breath 145 54%

Fatigue/Weakness 180 40%

Chills 99 37%

Myalgias 96 36%

Rhinorrhea 96 36%

Sore throat 84 31%

Headache 83 31%

Vomiting 78 29%

Wheezing 64 24%

Diarrhea 64 24%

Source: CDC. http://www.cdc.gov/h1niflu/surveillanceqa.htm

Emergency Warning Signs . In adults:

• Difficulty breathing or shortness of breath

• Pain or pressure in the chest or abdomen

• Sudden dizziness • Confusion • Severe or persistent vomiting • Flu-like symptoms improve but then

return with fever and worse cough

SYMPTOMS IN CHILDREN • Fast breathing or trouble breathing • Red or grey rash on skin • Not drinking enough fluids • Not waking up or not interacting • Being so irritable that the child does not want to

be held • Flu-like symptoms improve but then return with

fever and worse cough • Fever with a rash

Emergency warning signs in children

Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Severe or persistent vomiting Not waking up or not interacting Irritable, the child does not want to be held Flu-like symptoms improve but then return

with fever and worse cough

HIGH RISK CASES Adults 65 years and older

Children younger than 5 years old, but especially children younger than 2 years old

Pregnant women and women up to 2 weeks after the end of pregnancy

Asthma , Chronic lung disease (COPD] and cystic fibrosis

DIABETES

congestive heart failure and coronary artery disease)

Morbid obesity

Kidney disorders

Liver disorders

Weakened immune system due to disease or medication

(such as people with HIV or AIDS, or cancer, or those on chronic steroids)

Neurological and neurodevelopment conditions

Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders)

Blood disorders (such as sickle cell disease

People younger than 19 years of age on long-term aspirin therapy

Smoking and InfluenzaSome research studies show an increase in influenza

infections among smokers compared to nonsmokers.

There is a higher mortality rate for smokers than nonsmokers from influenza.

Diagnostic Tests Influenza

Diagnostic Tests

Method Availability TypicalProcessing

Time2

Sensitivity3 for

H1N1influenza

Distinguishes H1N1

influenza from other influenza A

viruses?

Rapid influenza diagnostic tests (RIDT)4

Antigen detection Wide 0.5 hour 10 – 70% No

Direct and indirectImmunofluorescence

assays (DFA and IFA)5

Antigen detection Wide 2 – 4 hours 47–93% No

Viral isolation in tissue cellculture

Virus isolation Limited 2 -10 days - Yes 6

Nucleic acid amplification

tests (including rRT-

PCR) 7

RNA detection Limited8  48 – 96 hours

[6-8 hours toperform test]

86 – 100% Yes

Source: CDC

SAMPLE COLLECTION.Respiratory specimens including:

v bronchoalveolar lavage,

v tracheal aspirates,

v nasopharyngeal or oropharyngeal aspirates as washes, and

v nasopharyngeal or oropharyngeal swabs.

Swab specimens should be collected only on swabs with a synthetic tip (such as polyester or Dacron) and aluminium or plastic shaft.

Swabs with cotton and wooden shafts are not recommended. Specimens collected with swabs made of calcium alginate are acceptable.

BEST TIME TO TAKE SAMPLESample need to be collected within the first 4 to 5 days of illness (when an

infected person is most likely to be shedding virus).

• However, some persons, especially children, may shed virus for 10 days or longer.

• Before antiviral medications are administered

Throat Swab • Highest yield in detecting H1N1

influenza in suspected cases

• Have the patient open his/her mouth wide open.

• Sample should be collected from back of the throat near the tonsils.

Nasal / Nasopharyngeal Swab

Insert dry swab into nostril and back to nasopharynx

Leave in place for a few seconds. Slowly remove swab while slightly rotating it.

Use a different swab for the other nostril. Put tip of

swab into vial containing VTM

Nasal Swab is collected from the anterior turbinate.

ANTIVIRAL TREATMENTThere are two flu antiviral drugs recommended

Oseltamivir or Zanamivir

Use of anti-virals can make illness milder and recovery faster

They may also prevent serious flu complications

For treatment, antiviral drugs work best if started soon after getting sick (within 2 days of symptoms)

Source: CDC

Source: CDC

OSELTAMIVIR (TAMIFLU) ZANAMIVIR (RELENZA)Treatment Prophylaxis Treatment Prophylaxis

ADULTS 75 mg capsule twice per day for 5 days

75 mg OD for 7-10 days

Two 5 mg inhalations (10 mg total) BD

Two 5 mg inhalations (10 mg total) OD

CHILDREN 15 kg or less: 30 mg BD

30 mg OD Two 5 mg inhalations (10 mg total) BD (age, 7 years or older)

Two 5 mg inhalations (10 mg total) OD (age, 5 years or older)

15–23 kg: 45 mg BD

45 mg OD

24–40 kg: 60mg BD

60 mg OD

>40 kg: 75mg BD

75 mg OD

ANTIVIRAL PROTECTION

OSELTAVIR(PRODRUG) MECHANISM OF ACTIONin the LIVER  it is hydrolyzed to its active metabolite - the free Oseltamivir carboxylate.Oseltamivir is a competitive neuramidase inhibitor. By blocking the activity of the enzyme, oseltamivir prevents new viral particles from being released through the cleaving of terminal sialic acid on glycosylated hem agglutinin and thus fail to

facilitate virus release. PHARMACOKINETICSIts Oral bioavailability is over 80% and is extensively metabolised to its active form upon first-pass through the liver.[Its half-life is about 1–3 hours and its active metabolite has a half-life of 6–10 hours.It is predominantly ELIMINATED IN THE URINE as the active carboxylate metabolite (>90% of oral dose)

MOST COMMON SIDE EFFECTS: Nausea, vomiting, abdominal pain, ear disorder, and diarrhea

DRUG INTERACTIONS: Co administration of oseltamivir and probenecid resulted in reduced clearance of Oseltamivir carboxylate by approximately 50% and a corresponding approximate two-fold increase In the plasma levels of oseltamivir carboxylate

Oseltamivir, zanamivir, rimantadine, and

amantadine are “Pregnancy Category C” few adverse events have been reported occasionally in pregnant women who took these medications, no causal relation between the use of these medications and these adverse events has been established . In addition, fever can cause adverse fetal outcomes, and reducing fever, whether directly by using antipyretics, or indirectly by reducing the duration and severity of symptoms with antiviral medications, might reduce this risk

. One retrospective cohort study found no evidence of an association between oseltamivir use during pregnancy and a variety of adverse events, including preterm birth, premature rupture of membranes, increased duration of hospital stay for mother or neonate, malformations, or fetal weight .

Oseltamivir is preferred for treatment of pregnant women.

.

PREGNANT WOMEN

PREVENTION

Recent studies* by CDC researchers and other experts indicate that flu vaccine reduces the risk of doctor visits due to flu by approximately 60% among the overall population when the vaccine viruses are like the ones spreading in the community.

Live Attenuated (Human) Influenza Vaccine

NASOVAC-S, Influenza Vaccine, (Human), freeze dried is a live trivalent vaccine for administration by intranasal spray

COMPOSITION[Propagated in Embryonated hen eggs]Each vial of single dose (0.5 ml) contains:

A(H1N1) Strain –

A/17/California/2009/38 (H1N1)* Not less than 107 EID 50A(H3N2) Strain

- A/17/Texas/2012/30 (H3N2)*     Not less than 107 EID 50B Strain

- B/60/Massachusetts/2012/10*       Not less than 106.5 EID 50

Reconstitute with Sterile Water for Inhalation USP

Dose: 0.5 ml intranasal (spray 0.25 ml per nostril)

The diluent supplied is specially designed for use with the vaccine. Only this diluent must be used to reconstitute the vaccine. Do not use diluents from other types of vaccine or from other manufacturers.Using an incorrect diluent may result in damage to the vaccine and/or serious reactions to those receiving the vaccine. Diluent must not be frozen, but should be kept cool.

ADVERSE REACTIONSLocal : Nasal discomfort, stuffy nose, sneezing, runny nose, loss of smell, red eyes, chills, facial swelling.Systemic : Fever, headache, fatigue, myalgia, arthralgia, irritability, loss of appetite, sore throat, cough, wheezing, nausea.

Nasal Spray Flu Vaccine

The nasal spray vaccine is approved for use in people 2 years through 49 years of age.

CONTRAINDIACTED IN:

Children younger than 2 years & Adults 50 years and older

People with a history of severe allergic reaction to any component of the vaccine or to a previous dose of any influenza vaccine

People who are allergic to eggs

Children or adolescents (2 years through 17 years of age) on long-term aspirin treatment.

Pregnant women

Children 2 years through 4 years who have asthma or who have had a history of wheezing in the past 12 months.

People who have taken influenza antiviral drugs within the previous 48 hours.

severely immunocompromised persons

STORAGE

2 - 8ºC (35-46ºF)

Difference in the efficacy of intranasal and

injectable flu vaccines ?

Several studies have proved that the clinical efficacy

of intranasal vaccine is superior to that of injectable

vaccine.

Injectable vaccines protect only at the level of the

blood by producing antibodies. While the intranasal

vaccine offers protection at two levels viz the local

level mucosal immunity (the nasal tract) and the

blood by producing antibodies. Due to this, when the

disease virus attacks it gets neutralized at its points of

entry i.e. the nasal tract. If it does manage to pass the

first line of defense, it gets neutralized in the blood.

If a person is protected with an injectable vaccine and

the virus attacks, then the virus will enter through

nose, initially multiply, infect and then its gets

neutralized when it reaches the blood. The person

will be protected overall but may spread the disease

in the initial period.

VACCINATE EVERY YEAR ?

The flu viruses are constantly changing .Generally new influenza virus strains circulate every flu season. Each Year, before flu season, the most recent circulating viruses are identified by the World Health Organization [WHO] and included in a new vaccine formula order to offer the best protection.

FLU COMPLICATIONSMost people who get influenza will recover in a few days

to less than two weeks, but some people will develop complications (such as pneumonia) as a result of the flu, some of which can be life-threatening and result in death.

Pneumonia, bronchitis, sinus and ear infections are examples of complications from flu. The flu can make chronic health problems worse.

For example, people with asthma may experience asthma attacks while they have the flu, and people with chronic congestive heart failure may experience worsening of this condition that is triggered by the flu.

COMPLICATIONS.Pulmonary complications

Primary viral pneumonia

Combined viral bacterial pneumonia

Secondary bacterial pneumonia.

ARDS

Extra pulmonary complications.

Viremia

Myositis

Cardiac involvement

Reye’s syndrome

CNS involvement

Toxic shock syndrome.

N95 masks do not provide complete protection, they are a valuable layer of defense.

Influenza viruses are usually transmitted in two ways, direct transmission (touching an infected surface) or droplet transmission. The influenza virus does not transmit across long distances and doesn't survive well when exposed to air (single influenza viruses don't just float around by themselves).

"N95" is a NIOSH standard, meaning that the mask stops 95% of

particles 3 microns or larger in size.

The average influenza virus is about 0.12 microns in size.

The average sneezed/coughed droplet is over 10 microns in size.

The average droplet nucleus size is 5-10 microns in size.

N95 masks and the H1N1 virus.

Why The Flu Virus Is More Infectious In Cold Winter TemperaturesAt winter temperatures, the virus's outer covering, or

envelope, hardens to a rubbery gel that could shield the virus as it passes from person to person, the researchers have found. At warmer temperatures, however, the protective gel melts to a liquid phase. But this liquid phase apparently isn't tough enough to protect the virus against the elements, and so the virus loses its ability to spread from person to person.

OTHER REASONS During the winter, people spend more time indoors with the

windows sealed, so they are more likely to breathe the same air as someone who has the flu and thus contract the virus .

Days are shorter during the winter, and lack of sunlight leads to  low levels of vitamin D and melatonin, both of which require sunlight for their generation. This compromises our immune systems, which in turn decreases ability to fight the virus .

The influenza virus may survive better in colder, drier climates, and therefore be able to infect more people .

Cold temperatures lead to drier air, which may dehydrate mucous membrane preventing the body from effectively defending against respiratory virus infections.

The virus may linger longer on exposed surfaces (doorknobs, countertops, etc.) in colder temperatures.

A seasonal decline in the amount of ultraviolet radiation may reduce the likelihood of the virus being damaged or killed by direct radiation damage or indirect effects (i. e. ozone concentration) increasing the probability of infection.

Source: Bean B, et al. JID 1982;146:47-51

Survival of Influenza Virus Surfaces and Affect of Humidity & Temperature*

Hard non-porous surfaces 24-48 hours

Plastic, stainless steel

Recoverable for > 24 hours

Transferable to hands up to 24 hours

Cloth, paper & tissue

Recoverable for 8-12 hours

Transferable to hands 15 minutes

Viable on hands <5 minutes only at high viral titers

Potential for indirect contact transmission

*Humidity 35-40%, Temperature 28C (82F)

Swine flu H1N1 BIRD FLU H5N1Swine flu spreads quickly as comparison to bird flu, but casualty rate not much high

Bird flu spreads very slowly, but has a high casualty rate.

Swine flu virus affects only the respiratory system.

The bird flu virus affects all systems of human body

 The main symptoms of swine influenza are vomiting and diarrhea. Apart from cough, fever, sore throat

Bird flu patients suffer from eye infections, pneumonia, and other severe problems.

Where as swine flu is transmitted from direct contact with pigs, waste matter contaminated by infected people

Bird flu is transmitted by direct contact with birds, their excretory products contaminated by infected people.

Pregnant women, persons with chronic medical conditions are most vulnerable target for swine influenza,

Small children and rural workers are soft target to get infected from bird flu.

Spread from person to person Less spread from person to person

SAFTEY MEASURES TO PREVENT INFECTION

Wear Glouses

Use Protective Eye Wear (Goggles)/Face Shields

Person Must Wash Their Hands Often – Especially After Handling Infectious Materials And , Before Leaving The Laboratory Working Areas, And Before Eating.

Appropriate Disinfectants

70 % Ethanol5 % Lysol10 % Bleach

.

Hand WashingWet hands with clean (not hot)

waterApply soapRub hands together for at least

20 secondsRinse with clean waterDry with disposable towel or

air dryUse towel to turn off faucet

Good Health Habits Can Help Stop flu

1. Avoid close contact.2. Stay home when you are sick. 3. Cover your mouth and nose.

4. Clean your hands. WITH alcohol-based hand rub.5. Avoid touching your eyes,

nose or mouth..Clean and disinfect frequently

touched surfaces at home, work or school, especially when someone is ill.

Get plenty of sleep, be physically active, manage your stress, drink plenty of fluids, and eat nutritious food.

Summary

• WHO raised the alert level to Phase 6 on June 11, 2009

• Influenza transmission remains active in much of western and central Asia and there is evidence of pandemic virus circulation in most regions of Africa

• The overall global case-fatality is ~1%

• Symptoms mimic seasonal flu

• 1:1 Male:Female Ratio

• Globally– Number of deaths being reported is rising

• Vaccine – Total Adverse Events: 5.4% (0.3% fatal)

• Anti-virals (oseltamivir and zanamivir)– Oseltamivir resistance reported recently in immunocompromised patents

…….Thank u