Influenza

By Aweeshna Sharma MussafeerBy Aweeshna Sharma Mussafeer

ML 510, PFURML 510, PFUR

INTRODUCTION Influenza is an acute viral infection that Influenza is an acute viral infection that

spreads easily from person to person.spreads easily from person to person. Incubation period- 1 to 5 daysIncubation period- 1 to 5 days It circulates worldwide causing epidemics It circulates worldwide causing epidemics

and pandemics. and pandemics. affects anybody of any age group.affects anybody of any age group. Each year, seasonal influenza affects 5-15% Each year, seasonal influenza affects 5-15%

of the population in the northern hemisphere.of the population in the northern hemisphere. Influenza spreads around the world in Influenza spreads around the world in

seasonal epidemics, resulting in the deaths of seasonal epidemics, resulting in the deaths of between 250,000 and 500,000 people yearly.between 250,000 and 500,000 people yearly.

Causative Agent of Influenza

Caused by the virus belonging to the

MYXOVIRUS group which comprises of

Orthomyxovirus and Paramyxovirus

Influenza virus is an Orthomyxovirus

CAUSATIVE AGENT

RNA virus

Family:

Genus:

Types: Type A Type B

Influenza virus

Type C

Influenza C virus

ORTHOMYXOVIRIDAE

Structure of the influenza virion

Haemagglutinin(HA) and neuraminidase(NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear

Proteins(RNPs)

Surface glycoproteins

1. Haemagglutinin-H or HA

-responsible for pathogenicity of the virus-allows virus to adhere to endothelial cells in

the respiratory tract-main determinant of immunity

2. Neuraminidase-N or NA

-decreases viscosity of mucous,hence virus moves easily

-allows release of newly formed viruses within host

-determinant of disease severity

Influenza subgroupsInfluenza A

-highly infective-infects many species

-causes widespread epidemicsInfluenza B

-found only in humans-capable of producing severe disease

-causes regional epidemicsInfluenza C

-causes mild disease-humans are natural hosts, but isolates also found

in pigs-does not cause epidemics

The virus nomenclature

Classification of Influenza virus

Classified on the basis of hemagglutinin (HA) and neuraminidase (NA)

15 subtypes of HA and 9 subtypes of NA are known to exist in animals (HA 1-15,

NA 1-9)3 subtypes of HA (1-3) and 2 subtypes of NA (1-2) are human influenza viruses.

HA 5, 7, 9 and NA 7 can also infect humans

Nomenclature of Human Influenza Virus

Type Subtype Prototype A H1N1 A/PR/8/34

A/NJ/8/76 H2N2 A/JP/305/57 H3N2 A/HK/1/68

B None B/Lee/40 C None C/Taylor/47

Influenza A Virus-Undergoes antigenic shifts and antigenic drifts with the haemagglutinin and neuraminidase proteins.-Antigenic shifts of the haemagglutinin results in pandemics. -Antigenic drifts in the H and N proteins result in epidemics. -Usually causes a mild febrile illness.-Death may result from complications such as viral/bacterial pneumonia.

The influenza A virus can be subdivided into different serotypes based on the antibody response to these viruses. The 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 Swine Flu in 2009•H2N2, which caused Asian Flu in 1957•H3N2, which caused Hong Kong Flu in 1968•H5N1, which caused Bird Flu in 2004•H7N7, which has unusual zoonotic potential•H1N2, endemic in humans, pigs and birds•H9N2•H7N2•H7N3•H10N7

-infect people, birds, pigs, horses, seals, whales, and other animals.

-Main host: bird

Influenza A

Epidemiology Pandemics - influenza A pandemics arise

when a virus with a new haemagglutinin subtype emerges as a result of antigenic shift. As a result, the population has no immunity against the new strain. Antigenic shifts had occurred 3 times in the 20th century.

Epidemics - epidemics of influenza A and B arise through more minor antigenic drifts as a result of mutation.

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

2009 H1N1 “Swine Flu Mild pandemic

Epidemics Involve 10% - 20% of world’s population. Kill 500,000 to 1,000,000 people yearly. Predictable, yearly. Driven by “drift” mutations.(Mutations can

cause small changes in the hemagglutinin and neuraminidase antigens on the surface of the virus)

Changes confined to hemagglutinin (H)

and neuraminidase (N)

Pandemics Involve more than 25% of world’s population. Number of deaths varies. Unpredictable, sporadic. Driven by “shift” mutations.(acquirement of

completely new antigens—for example by reassortment between avian strains and human strains)

Adaptation of animal-like to human-like strains. Adaptation involves all 8 gene segments

(polygenic selection)

Example of driftAntigenic drift creates influenza viruses with slightly modified antigens,

A/Texas/1/77(H3N2) ---> A/Bangkok/1/79(H3N2)

Avian influenza(bird flu) All known viruses that cause influenza in

birds belong to the species influenza A virus. found chiefly in birds, but infections can occur in humans. Wild birds carry the viruses in their intestines, but usually do not get sick from them. Infected birds shed influenza virus in their

saliva, nasal secretions, and feces.

human contractions of the Avian flu are a result of either handling dead infected birds or from contact with infected fluids

Avian InfluenzaH5N1H5N1 An outbreak of Avian Influenza H5N1 occurred in

Hong Kong in 1997 where 18 persons were infected of which 6 died.

The source of the virus was probably from infected chickens and the outbreak was eventually controlled by a mass slaughter of chickens in the territory.

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

However, the strains involved were highly virulent for their natural avian hosts.

Where is H5N1 now?

H9N2

Several cases of human infection with avian H9N2 virus occurred in Hong Kong and Southern China in 1999.

The disease was mild and all patients made a complete recovery

Again, there was no evidence of reassortment

Swine Flu is a respiratory disease of pigs caused by

type A influenza virus that regularly causes outbreaks of influenza in pigs

high levels of illness and low death rates in pigs

change constantly.

As of 2009, the known SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H3N1, H3N2, and H2N3.

Can be transmitted to man by direct close regular contact with infected pigs but not by consuming infected meat.

Is the H1N1 swine flu viruses the same as human H1N1 viruses?

the H1N1 swine flu viruses are antigenically very different from human H1N1

Novel H1N1 Influenza

Novel H1N1 is a new influenza virus that is spreading from person-to-person.

The United States government has declared a public health emergency in the U.S. in response to the H1N1 outbreak.

The first cases of human infection with novel H1N1 influenza virus were detected in April 2009 in San Diego and Imperial County, California and in Guadalupe County, Texas.

The virus has spread rapidly.

Influenza Type B

Usually only found in humans not classified according to subtype cause human epidemics, but they have not

caused pandemics

Less common mutates at a rate 2–3 times slower than type

A and consequently is less genetically diverse, with only one influenza B serotype

a degree of immunity to influenza B is usually acquired at an early age (temporary immunity)

Influenza Type C

cause mild illness in humans do not cause epidemics or pandemics These viruses are not classified according to

subtype.

Risk Factor For Influenza

• 50 years of age and older• Long-term heart or lung problems• People that have kidney disease, cystic

fibrosis, anemia or immunology disorders can also easily get Influenza

Exposure to smoke, toxic fumes, industrial smoke and other environmental pollutants (injure airways and damage the cilia)

Travelling in Public Transport such as Buses, and Trains

Colds and flu's occur predominantly in the winter (higher concentrations of airborne viruses, Dry winter weather also dries up nasal passages while making them more susceptible to viruses)

Mode of transmission

AIR BORNE DIRECT CLOSE CONTACT

Route of transmission

droplets from coughing and sneezing. the viruses fly into the air along with

mucus, saliva and other secretions infects the nose, throat or lungs Also by close contact to infected person or

object

Influenza Transmission Large particle droplets, respiratory

secretionsCoughing, sneezing, talking

Viral replication occurs in the respiratory tract

Shedding of the virus peaks at 2 days after exposure and rapidly declines thereafter

Average duration of shedding: 4.8 days Longer periods of shedding in: children,

elderly, immunocompromised, chronic illnesses

Timely treatment has been shown to decrease amount of viral shedding

Symptoms of 2 Types of Influenza

H5N1 ( Avian Influenza) Fever Cough Sore Throat Muscle Aches Difficulty Breathing Diarrheal

H1N1 (Swine Influenza) Fever Cough Sore Throat Body Aches Runny Nose Extreme Fatigue Diarrheal Vomiting

Uncomplicated influenza: improve in 2-5 days

Complicated influenza: pneumonia (influenza, viral or bacterial), myositis, rhabdomyolysis, CNS involvement (encephalitis, Guillain-Barre), exacerbation of chronic disease

complicationsIn young children: Middle ear infections Seizures due to high fever

Pulmonary :

chronic bronchitis, emphysema, asthma, cystic fibrosis, pneumonia (due to bacterial superinfection)

Obstruction of air flow to lungs, hence cardiac arrhythmias, shock.

Tacchypnoe and cyanosis

Cardiac: Myocarditis and pericarditis

Destruction of skeletal muscles

Inflammation of the brain and spinal cord rarely.

Reye’s syndrome causing fatty accumulation and brain edema, severe nausea and vomiting.

Other complications

Haemorrhagic syndrome Epistaxis Rashes in genitals Lung edema Brain edema Shock Secondary infections eg pneumonia

emergency warning signs in H1N1 infection 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

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

Diagnosis

Often made clinically during (especially during an outbreak)“Acute febrile illness”“Fever and cough within 48hrs of

exposure”“Fever, malaise, or chills in the elderly”

Lab tests Done during “off season” or when results

would change managementRapid antigen test ImmunofluorescenceRT-PCRViral cultureSerologic testing

Treatment Neuraminidase inhibitors

Active against Influenza A and B Oseltamivir Zanamivir

Adamantanes Only active against Influenza A Amantidine Rimantadine

Neuraminidase Inhibitors

Work by inhibiting neuraminidase Oseltamivir (Tamiflu)

Shortens duration of symptoms, reduces severity, complication rates, mortality, and hospital stay

SE: N/V, delerium (in Japan study only)

ZanamivirContraindicated in asthma, chronic

respiratory conditionsReduces duration of symptomsSE: bronchospasm, decline in respiratory

function

Neuraminidase Inhibitor Resistance Resistance caused by a histidine to tyrosine

substitution of the neuraminidase Prior to 2007: 1-5% resistance 2007-2008: 20% resistance; can be

transmitted between individuals (seen in some with no prior exposure to the medication)

2008-2009: 97% resistance to certain influenza strains

Oseltamivir resistance primarily observed with Influenza A, but also seen with Influenza B virus

Adamantanes

Block the viral M2 protein ion channel which prevents fusion of the virus and host-cell membrane

Amantadine and Rimantadine Shown to reduce duration of symptoms SE: CNS toxicity

High rates of resistance Not recommended for routine use for

influenza Exception: can be used in combination with Oseltamivir

when there is contraindication to Zanamivir (chronic cardiopulmonary disease, asthma)

Adamantane Resistance

Spontaneous or after initiation of treatment Point mutation in the codons for amino

acids of the M2 protein 1994-1995: 0.4% resistance

2003-2004: 12.3% resistance Higher resistance in Asia

Able to purchase OTCGiven to poultry and livestockOveruse during SARS outbreak

2005-2006: up to 92% resistance

Other treatment:Zanamivir or combination of oseltamivir

+ adamantases used when there is a high level of seasonal H1N1 resistant to Oseltamivir

Isolation:Standard and droplet precautionsFor 5 days after onset in

immunocompetentFor duration of illness in

immunocompromised

Ribavirin is thought to be effective against both influenza A and B.

Prevention

Inactivated split/subunit vaccines are available against influenza A and B.

The vaccine is normally trivalent, consisting of one A H3N2 strain, one A H1N1 strain, and one B strain.

The strains used are reviewed by the WHO each year.

The vaccine should be given to debilitated and elderly individuals who are at risk of severe influenza infection.

Amantidine can be used as an prophylaxis for those who are allergic to the vaccine or during the period before the vaccine takes effect.

SELF PROTECTION

Take these everyday steps to protect your health Wash your hands often with

soap and warm water,

especially after you cough

or sneeze. Wash for 15 – 20

seconds. Alcohol-based hand

wipes or gel sanitizers are also

effective.

Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it.

Avoid touching your eyes, nose or mouth.

Germs spread this way.

Avoid contact with sick people.

GET VACCINATED

Vaccine of influenza

There have two types of vaccines:

1. The “flu shot”

2. The nasal-spray flu vaccine

Each vaccine contains three influenza viruses-one A (H3N2) virus, one A (H1N1) virus, and one B virus.

About 2 weeks after vaccination, antibodies that provide protection against influenza virus infection develop in the body.

The "flu shot"— an inactivated vaccine (containing killed virus) that is given with a needle, usually in the arm. The flu shot is approved for use in people older than 6 months, including healthy people and people with chronic medical conditions. .

The nasal-spray flu vaccine — a vaccine made with live, weakened flu viruses that do not cause the flu (sometimes called LAIV for “live attenuated influenza vaccine” or FluMist®). LAIV (FluMist®) is approved for use in healthy* people 2-49 years of age who are not pregnant.

People who should get vaccinated each year are:

1. Children aged 6 months up to their 19th birthday

2. Pregnant women

3. People 50 years of age and older

4. People of any age with certain chronic medical conditions

1. People who live in nursing homes and other long-term care facilities

2. People who live with or care for those at high risk for complications from flu

Chinese inspectors on an airplane, checking passengers for fevers, a common symptom of swine flu.

WEAR YOUR MASK

Parainfluenza Virus

ssRNA virus enveloped, pleomorphic morphology 5 serotypes: 1, 2, 3, 4a and 4b No common group antigen Closely related to Mumps virus

Clinical Manifestations

Croup (laryngotracheobronchitis) - most common manifestation of parainfluenza virus infection. However other viruses may induce croup e.g. influenza and RSV.

Other conditions that may be caused by parainfluenza viruses include Bronchiolitis, Pneumonia, Flu-like tracheobronchitis, and Corza-like illnesses.

Laboratory Diagnosis Detection of Antigen - a rapid diagnosis can

be made by the detection of parainfluenza antigen from nasopharyngeal aspirates and throat washings.

Virus Isolation - virus may be readily isolated from nasopharyngeal aspirates and throat swabs.

Serology - a retrospective diagnosis may be made by serology. CFT most widely used

Management

No specific antiviral chemotherapy available.

Severe cases of croup should be admitted to hospital and placed in oxygen tents.

No vaccine is available.

THANK YOU ! ! !