“This is scary and we don’t know…” “We don’t know the timing of the next pandemic, how...

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“This is scary and we don’t know…” “We don’t know the timing of the next pandemic, how severe it will be. We don’t know what drugs will work. We don’t have a vaccine. Yet we are telling everyone to prepare for a pandemic. It’s tricky…This is scary and we don’t know…that’s the message.” Dick Thompson World Health Organization December 2005

Transcript of “This is scary and we don’t know…” “We don’t know the timing of the next pandemic, how...

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“This is scary and we don’t know…”

“We don’t know the timing of the next pandemic, how severe it will be. We don’t know what drugs will work. We don’t have a vaccine. Yet we are telling everyone to prepare for a pandemic. It’s tricky…This is scary and we don’t know…that’s the message.”

Dick Thompson

World Health Organization

December 2005

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INFLUENZA - the name

• Influenza is Italian for "influence", Latin: influentia. It used to be thought that the disease was caused by a bad influence from the heavens.

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• Flu sometimes is confused with the common cold. However, the flu is caused by influenza virus, and is a much more severe disease than the common cold, which is caused by a different type of virus. Influenza is a more severe viral infection of the respiratory tract that shows the additional symptoms to those of the common cold (rapidly rising fever, chills, and body and muscle aches).

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INFLUENZAINFLUENZA

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• Influenza is an acute systemic viral disease.

• Has very serious complications.

• Caused by influenza virus.

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1. \Family is Orthomyxoviridae

2. Influenza family which is subdivided into 3 genera: A, B, and C, based on antigenic differences in the nucleoprotein (NP) and matrix (M) protein.

2. Influenza A viruses are further characterized by antigenic differences associated with the Haemagglutinin (HA) and Neuraminidase (N) glycoproteins; there are at least 15 subtypes

of H and 9 subtypes of N proteins in influenza A virus. 3. All subtypes have been described in birds and some of them

have been found in mammals.

ClassificationClassification

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Humans Swine Birds Horses Seals

Type A Humans

Type C

Type B

Humans Swine

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Virus characteristics

1. Virion is 80-120 nm in diameter), enveloped, spherical to slightly pleomorphic in shape.

2. Underline the envelope is the Matrix ( M1 & M2)

2. Genome consists of 8 segments of ss RNA in A& B and 7 segments in C

3. The envelope contains 2 glycoproteins: H (hemagglutinin), and N (neuraminidase)

4. associated with the genome is nucleoprotein (NP)

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ORTHOMYXOVIRUSES

M1 protein

helical nucleocapsid (RNA plus NP protein)

HA - hemagglutinin

polymerase complex

lipid bilayer membrane

NA - neuraminidase

Type A, B, C : NP, M1 protein Sub-types: HA or NA protein

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Influenza virus

Hemagglutinin

Neuraminidase

A/Beijing/32/92 (H3N2)

Virus type

Geographic origin

Strain number

Year of Isolation

Virus subtype

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• Influenza A is classified into subtypes based on HA & NA

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DISEASE

• Influenza A virus cause – worldwide epidemics (pandemic) – major outbreaks of influenza

• occurs virtually every year.

• Influenza B virus cause – major outbreaks of influenza

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Nomenclature

A/equine/Saskatoon/1/90(H3N8)

group

species

locationIsolate number

year

Serotype of HA and N

•A/equine/Prague/1/56(H7N7)•A/fowl/Hong Kong/1/98(H5N1)•A/swine/Lincoln/1/86(H1N1)

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• Seasonal (human) Influenza ( H1N1)EndemicStrain varies slightly year to year

• Avian Influenza (H5N1)May be reservoir for completely new strains in humansCan be Highly Pathogenic Avian Influenza (HPAI)

• Pandemic Influenza (H1N1)Global epidemic of new influenza A subtype in humans

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ANTIGENIC CHANGES

• Influenza viruses especially type A show changes in antigenicity of hemagglutinin (H) and neuraminidase (N) proteins.

• Antigenic shifts: – major changes based on the reassortment of RNA

segments. It occurs only with influenza A. – Other theories of antigenic shift includes:

• Recirculation of existing subtypes• Gradual adaptation of animal viruses to human transmission

• Antigenic drifts: – minor changes based on mutations in the RNA genome.

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• Animal viruses (aquatic birds, chicken, swine) are the source of RNA segments that encode antigenic shift variants.

• Because influenza B virus is only a human virus, there is no animal source of new RNA segments. Influenza B virus shows only antigenic drift, but not shift.

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Antigenic Variation

• Due to:-

• A. genome is segmented

• Can infect wild range of different species.

• It is RNA virus ( mutation more common).

• Two forms

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1. Antigenic shift

• Major change.

• Occurs in influenza A only.

• Result in a new subtype.

• Associated with pandemic

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Mechanism

• Co-infection with 2 different subtypes usually avian and human occurs in pigs ( mixing vessel) .(same cell 2 subtypes)

• Genetic reassortment occurs ( swapping of the genes) results in development of a new subtype

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Reassortment

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Pigs Serve As Mixing Vessels for reassortants • Pig cells contain receptors for both human and avian

viruses.

Aquatic birds and domestic Pigs HumanPoultry (Human virus)(Avian virus)

Human

(reassortant virus)

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A / PHILIPPINES / 82 (H3N2)

• A group antigen of influenza A

• Philippines / 82 location and year the virus isolated

• H3N2 Hemagglutinin and Neuraminidase types

• H1N1 and H3N2 strains of influenza A are the most common types at this time and are the strains included in the current vaccine.

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Past Antigenic Shifts

1918 H1N1 “Spanish Influenza” 20-40 million deaths

1957 H2N2 “Asian Flu” 1-2 million deaths

1968 H3N2 “Hong Kong Flu” 700,000 deaths

1977 H1N1 Re-emergence No pandemic

At least 15 HA subtypes and 9 NA subtypes occur in nature. Up until 1997, only viruses of H1, H2, and H3 are known to infect and cause disease in humans.

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2. Antigenic drift

• Minor change.

• Occurs in influenza A & B

• Occurs between epidemics.

• Results in seasonal localized outbreaks.

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Mechanism

• Due to cumulative point mutations in the HA gene

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TransmissionTransmission

Airborne – droplets – esp. crowded populations in enclosed spaces

Direct contact – virus may persist on object for hours to days – esp. in cool, dry areas

Incubation – 1 – 3 days Communicable – 1-2 days before onset of

symptoms and 4-5 days after onset Possibly up to 21 days in < 12 y.o. or adults w/ avian

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Influenza spread

Courtesy of Centers for Disease Control and Prevention

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Clinical Features

• Incubation period 24 – 48 hours

• Sudden onset of fever with chills , myalgias, headache, dry cough, photophobia, sore throat

• Diarrhoea and vomiting may occur

• Resolve spontaneously in 4 – 7 days. although cough and malaise can persist for >2 weeks. Influenza B is similar to A, but influenza C is usually subclinical or milder in nature.

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Complications

• Tend to occur in the

a.young,

b. elderly,

c. pregnants

d.persons with chronic cardio-pulmonary diseases.

e.Persons with chronic diseases :DM,renal,liver

f. Immunocompromized patients

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COMPLICATIONS

• Tracheobronchitis and bronchiolitis • Croup• Primary viral pneumonia • Secondary bacterial pneumonia

– usually occurs late in the course of disease, after a period of improvement has been observed for the acute disease. S. aureus is most commonly involved although S. pneumoniae and H. influenzae may be found.

• Myositis and myoglobinuria

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• Reye's syndrome– Reye's syndrome is characterized by encephalopathy and

fatty liver degeneration. It occurs in children with viral infection and are taken aspirin to reduce fever. The disease had been associated with several viruses; such as influenza A and B, Coxsackie B5, echovirus, HSV, VZV, CMV and adenovirus.

• Myocarditis and pericaditis

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LABORATORY DIAGNOSIS

• Virus Isolation – Specimens :Throat swabs, Nasopharyngeal aspirate (NPA)

and nasal washings may be used for virus isolation.. Influenza viruses isolated from embryonated eggs or tissue culture can be identified by serological or molecular methods.

• Rapid Diagnosis by Immunoflurescence (Antigen detetection)

– cells from pathological specimens may be examined for the presence of influenza A and B antigens by indirect immunofluorescence.

– Nucleic acid detection using PCR ( same specimen as above)

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• Serology – Demonstration of a rise in serum antibody to the infecting

virus

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TREATMENT

• Amantidine • The only effective against influenza A.• Act at the level of virus uncoating inhibit M2

protein.• Both therapeutic and prophylactic effects. • Significantly reduces the duration of fever (51

hours as opposed to 74 hours) and illness. • 70% protection against influenza A when given

prophylactically. • Rimantadine is an amantadine derivative but not

as effective as amantadine and less toxic.

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• Neuraminidase inhibitors - zanamivir (given by inhalation)- oseltamivir (orally)

Used for influenza A and B including pandemic H1N1

Used for treatment and prophylaxis• To be maximally effective the drugs

must be administered very early in the disease.

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Anti-viral drugs: General background

Amantadine Rimantadine Zanamivir Oseltamivir

Type of Influenza virus infection indicated for use

Influenza A Influenza AInfluenza A Influenza B

Influenza A Influenza B

Administration oral oraloral inhalation

oral

Ages approved for treatment of flu

1 year 14 year 7 years 18 years

Ages approved for prevention of flu

1 year 1 year not approved not approved

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PREVENTION

• Vaccine• Protection lasts only 6 months• Yearly boosters are recommended• Should be given to people

– Older than 65 years– With chronic respiratory diseases– With chronic cardiovascular diseases.

• Immunity to Influenza – Antibody against hemagglutinin (H) is the most important

component in the protection against influenza viruses.

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Influenza Vaccines

• Though existing vaccines are continually being rendered obsolete as viruses undergo antigenic drift and shift.

• Yet controlled trials of influenza vaccines indicate that a moderate degree of protection (50-80%) is attainable.

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1) Inactivated influenza vaccines

• Is a trivalent vaccine containing (H1N1 ,H3N2 and B )

• Vaccines are either whole virus (WV) vaccine which contains intact, inactivated virus

• or subvirion (SV) vaccine:– contain purified HA and NA glycoproteins.

.

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2) Live influenza vaccines:

• The only feasible strategy to develop a live-virus vaccine is to devise a way to transfer defined attenuating genes from an attenuated master donor virus to each new epidemic or pandemic isolate.

• A cold-adapted influenza virus (able to grow at 25C but not at 37C) introduced intranasally should replicate in the nasopharynx but not in the lower respiratory tract, its multiplication stimulate the local production of IgA.

• ( Flumist)

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Good luck

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AVIAN INFLUENZA

• Avian influenza A viruses usually do not infect humans

• Rare cases of human infection with avian influenza viruses have been reported since 1997 with avian influenza A (H5N1H5N1) viruses

• All strains of the infecting virus were totally avian in origin and there was no evidence of reassortment.

• Infection in humans are thought to have resulted from direct direct contact with infected poultrycontact with infected poultry or contaminated surfaces.

• To date, human infections with avian influenza A viruses have not resulted in sustained human-to-human transmission.

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PICORNAVIRUSES

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PICORNAVIRUSES

• Small (20 – 30 nm) non–enveloped viruses, with icosahedral nucleocapsid and ssRNA genome with positive polarity.

• Includes two groups: • EnterovirusesEnteroviruses

– Enteroviruses include poliovirus, coxsackieviruses, echovirus and hepatitis A virus.

– replicate optimally at 37 ºC– Enteroviruses are stable under acid conditions (pH 3 – 5)

• RhinovirusesRhinoviruses– Rhinoviruses grow better at 33 ºC in accordance with the lower

temperature of the nose.– Rhinoviruses are acid – labile.

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RHINOVIRUSES

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RHINOVIRUSES

• Common cold accounts for 1/3 to 1/2 of all acute respiratory infections in humans.

• Rhinoviruses are responsible for 50% of common colds, coronaviruses for 10%, adenoviruses, enteroviruses, RSV, influenza, parainfluenza can also cause common cold symptoms indistinguishable form those caused by rhinoviruses and coronaviruses.

• Common cold is a self-limited illness.• More than 100 serologic types of rhinoviruses

(No vaccine)

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TRANSMISSION

• Directly from person to person via respiratory droplets

• Indirectly in which droplets are deposited on the hands or on a surface such as table and then transported by fingers to the nose or eyes.

• An individual may suffer 2 to 5 episodes of colds per year. The primary site of rhinovirus infection is in the nasal epithelium. Rhinoviruses rarely cause lower respiratory infection.

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CLINICAL FINDINGS

• Incubation period: 2 – 4 days

• Sneezing• Nasal discharge• Nasal obstruction• Sore throat• Cough• Headache • Lasts for 1 week

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COMPLICATIONS

• Acute bacterial sinusitis – The major causes are Pneumococcus, Hemophilus

influenza, Moraxella, and Staphylococci.

• Acute bacterial otitis media – mainly a problem in children

• Asthma attacks in children

• Exacerbation of chronic bronchitis

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LABORATORY DIAGNOSIS

• Usually, common cold does not require laboratory investigation

• Cell culture isolation from nasal secretion

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TREATMENT

• Cold treatments recommended include the following:– Antihistamines– Nonsteroidal antinflammatory drugs– Decongestants (vasoconstrictors)– Cough suppressants (narcotics)

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CORONAVIRUSES 

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CORONAVIRUSES

• The group was so named because of the crown-like projections on its surface.

• At present, at least 10 species are recognized, of which human coronavirus is one. The other viruses are found in animals.

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PROPERTIES

• ssRNA enveloped viruses of pleomorphic morphology

• 60 to 220nm in diameter. • Positive stranded RNA; helical symmetry • Three antigenic molecules are found in the

virions i.e. nucleocapsid, surface projection and transmembrane proteins. The main antigenic determinants reside on the surface projections.

• Human coronavirus strains fall into serological groups, which are named OC43, and 229E.

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EPIDEMIOLOGY

• Human coronavirus infections occur during the winter and early spring.

• High infection rates during the year are caused by either 229E or OC43 group viruses. This pattern is observed throughout the world.

• Human coronaviruses are responsible for 10 - 30% of all common colds.

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DIAGNOSIS AND TREATMENT

• Laboratory diagnosis is not attempted.

• Coronaviruses have fastidious growth requirement in cell culture.

• No antiviral drugs against coronaviruses are available.

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OTHER CAUSES OF COMMON COLD SYNDROME

• Coxsackievirus– Herpangina (severe sore throat with vesiculoulcerative

lesions)– Pleurisy– common cold syndrome

• Adenovirus– Pharyngitis– common cold syndrome– Bronchitis– pneumonia (types 3, 4, 7 and 21)

• Influenza C

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Definition of Terms

• Seasonal (human) Influenza– Endemic– Strain varies slightly year to year

• Avian Influenza– May be reservoir for completely new strains in

humans– Can be Highly Pathogenic Avian Influenza (HPAI)

• Pandemic Influenza– Global epidemic of new influenza A subtype in

humans

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Three Types of Influenza Seasonal influenza refers to the periodic outbreaks of respiratory illness in the fall and winter.

Avian influenza - also known as the bird flu - is caused by virus that infects wild birds and domestic poultry. Two types: Low pathogenic avian influenza virus (H5 and H7) and highly pathogenic avian or bird influenza of the H5N1 strain.

Pandemic influenza refers to a worldwide outbreak of influenza among people when a new strain of the virus emerges that has the ability to infect humans and to spread from person to person.

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What is seasonal flu?

• Contagious, respiratory illness

• Affects 5-20% of population each year

• Kills approximately 36,000 every year

• Can be prevented with a vaccine

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Bird or Avian Flu – H5N1

• A powerful virus• Spread by migratory

birds• Transmitted from

birds to humans and other mammals

• Kills 60% of its victims• It continues to change

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H5N1 Transmission• Bird Human

– Handling live diseased birds– Preparing dead diseased birds– Eating undercooked poultry

• Human Human– Rare

• 2004 Thailand• 2006 Indonesia

www.bbc.co.uk

Courtesy of Dr. Steve Lawrence

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What is Pandemic Influenza?

An influenza pandemic occurs when a new influenza virus appears against which the human population has no immunity, resulting in several, simultaneous epidemics worldwide with enormous numbers of deaths and illness.

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How Influenza Can Spread Between People

• Influenza is thought to be primarily spread through large droplets (droplet transmission) that directly contact the nose, mouth or eyes.

• Droplets are produced when infected people cough, sneeze or talk, sending the relatively large infectious droplets and very small sprays (aerosols) into the nearby air and into contact with other people.

• Large droplets can only travel a limited range; therefore, people should limit close contact (within 6 feet) with others when possible.