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ABCs of Influenza and Pandemics

Rapid Response Team Training in Southeast Asia

Photo: Cynthia Goldsmith

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Learning Objectives

• Describe the characteristics of influenza infection in humans

• Understand different types of influenza viruses and how they can infect humans and animals

• Describe the ways that influenza viruses can change or mutate

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Learning Objectives

• Describe the epidemiology of influenza and contrast pandemic influenza with seasonal influenza outbreaks

• Understand the recent history of avian influenza outbreaks in humans

• Describe the epidemiology and clinical characteristics of the H5N1 outbreak in humans

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Session Overview

• Influenza infection in humans

• Influenza virus

• Influenza epidemiology

• Avian influenza infection in humans

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Influenza Infection in Humans

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Key Characteristics

Influenza is usually a respiratory infection

Transmission– Highly contagious – Primarily through contact with

respiratory droplets – Transmission from objects possible

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Key Characteristics

Communicability– Transmission 1 - 2 days

before to 4 - 5 days after onset of symptoms (about 3 – 5 days of viral shedding)

– Peak viral shedding occurs on day 1 of symptoms

– Infants, children and the immunocompromised may shed the virus longer

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Incubation period– Time from exposure to onset of symptoms– 1 to 5 days (average = 2 days)

Seasonality– In temperate zones, sharp peaks in winter

months – In tropical zones, circulates year-round

with seasonal increases

Key Characteristics

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Typical Signs and Symptoms

Rapid onset of symptoms– Fever / Chills

– Body aches

– Sore throat

– Non-productive cough

– Runny nose

– Headache

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Groups at Risk for Serious Complications

Complications– Pneumonia, worsening of chronic lung and

heart problems, and death

High Risk Groups– Persons 65 years and older– Persons with chronic diseases – Infants between 6 months and 2 years– Pregnant women– Nursing home residents– Children on long-term aspirin therapy

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Vaccination

• Influenza vaccine is the best prevention for seasonal influenza.

• Inactivated viruses in the vaccine developed from three circulating strains (generally 2 Type A and 1 Type B strain)– Therefore, seasonal “flu shot” only works for 3 influenza

subtypes and will not work on pandemic strains.

• In temperate zones, the vaccine is administered intramuscularly to all high risk persons > 6 months

• Limited supply of intranasal vaccine is available

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Influenza Virus

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Influenza VirusTypes A and B

Type A Type B

Can cause significant disease

Generally causes milder disease but may also cause severe disease

Infects humans and other

species (e.g., birds)

Limited to humans

Can cause epidemics and pandemics (worldwide epidemics)

Generally causes milder epidemics

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Influenza A Virus Subtyping

• Influenza A subtypes are determined by two surface glycoproteins

–Hemagglutinin (HA)

–Neuraminidase (NA)

• 16 HA’s and 9 NA’s

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Species Infected by Influenza A, HA and NA Subtypes

H15,16H14

H13

H12H11H10

H3

H2

H1

H9

H8

H7H6H5

H4

N9N8N7N6

N5

N3

N4

N2

N1

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Surface Protein Changes

Antigenic DRIFT

– Minor change in HA / NA

– Point mutations during replication, but subtype remains the same

– Continuous changes, so the virus avoids immunity

– Limited partial immunity may exist to changed virus

– Results in the need to update vaccines annually

Antigenic SHIFT

– Major change in HA / NA

– New subtype introduced

– Caused by genetic re-assortment when 2 subtypes infect a host simultaneously

OR

– Caused by direct transmission from birds or other animals to humans

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HumanHuman virusvirus

ReassortantReassortantvirusvirus

Non-humanNon-humanvirusvirus

Re-assortment and Direct Transmission

DIRECTDIRECT

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Influenza Epidemiology

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Epidemiology Terms

• Endemic– A disease that occurs at an expected constant

level in a population– “Background” level

Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm

Red line: Expected deaths each year

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Epidemiology Terms

• Epidemic– When the cases of a disease exceed what is

normally expected

• Pandemic– An epidemic that occurs over a large geographic

area, or across the whole world

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Impact of Seasonal Influenza

• An annual public health problem

• Substantial health impact– 10 - 35% of children each year– 5 - 20% of adults each year

• Substantial economic impact – Lost work / school days– Overwhelmed medical care systems

• High incidence and costs in tropical zones (e.g., Singapore, Hong Kong, Thailand)

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Seasonal Influenza – A public health problem

each year

– Usually some immunity built up from previous exposures to the same subtype

– Infants and elderly most at risk

– Result of Antigenic Drift

Influenza Pandemics– Appear in the human

population rarely and unpredictably

– Human population lacks any immunity

– All age groups, including healthy young adults, may be at increased risk for serious complications

– Result of Antigenic Shift

Seasonal Epidemics vs. Pandemics

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1918-19 Spanish Flu (H1N1)– ~ 40 million deaths worldwide

1957-58 Asian Flu (H2N2)– 1 - 2 million deaths worldwide

1968-69 Hong Kong Flu (H3N2)– ~ 700,000 deaths worldwide

Mortality Impact of Past Pandemics

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Timeline of Influenza Pandemics

H1

H3H2

1918Spanish

Influenza H1N1

1957Asian

InfluenzaH2N2

1968Hong KongInfluenza

H3N2

1915 1925 1935 1945 1955 1965 1975 1985 1995 2005

H7H5

Avian Influenza

H9

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WHO Stages of a Pandemic

• Inter-pandemic period

• Pandemic alert period

• Pandemic period

• Post pandemic period

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WHO Phases of a Pandemic

Inter-pandemic Period

Phase 1: No new Influenza virus subtypes in humans

Phase 2: No new virus subtypes in humans; animal subtype poses a risk of human disease

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Pandemic Alert Period

Phase 3: Human infection with novel virus; no instances of human-to-human spread

Phase 4: Small, localized clusters of human-to-human spread

Phase 5: Larger clusters, still localized; virus adapting to humans

WHO Phases of a Pandemic

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Pandemic Period

Phase 6: Increased and sustained transmission in the general population.

Post Pandemic Period

Recovery phase

WHO Phases of a Pandemic

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Avian Influenza

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Avian Influenza• Type A influenza

• Endemic in birds

• H5, H7 subtypes can cause serious disease or death in wild birds; often cause death in poultry

• Virus in saliva and feces of wild birds and poultry can be directly transmitted to humans and other animals

• Can contaminate clothing, equipment, water, feed

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Avian Influenza

• Low pathogenic AI (LPAI)– Most common influenza infection in birds– Causes mild clinical and unapparent infections– May be any subtype (H1 to H15)

• Highly pathogenic AI (HPAI)– Some H5 or H7 subtypes– Causes severe illness in poultry and often death– LPAI H5 or H7 subtypes can mutate

into HPAI H5 or H7 subtypes

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Avian Influenza in HumansYear Subtype Location Cases Deaths

1996 H7N7 United Kingdom 1 0

1997 H5N1 Hong Kong 18 6

1998 H9N2 China 6 0

1999 H9N2 Hong Kong 2 0

2002 H7N2 United States 1 0

2003 H7N2 United States 1 0

2003 H9N2 Hong Kong 1 0

2003 H5N1 Hong Kong 2 1

2003 H7N7 The Netherlands 89 1

2004 H7N3 Canada 2 0

2003-06 H5N1 Worldwide 228 130

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Incubation period likely 2 - 8 days but may be longer

Initial symptoms• High fever (>38 C)• Respiratory symptoms (e.g., cough, sore throat,

runny nose) • Muscle aches, headache• More rare: frequent watery diarrhea, abdominal pain,

vomiting

Source: The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian Influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85.

H5N1 Clinical Features

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Clinical course• Shortness of breath (Dyspnea)

• Clinical pneumonia with variable x-ray findings

• Acute Respiratory Distress Syndrome (ARDS)

• Case Fatality Rate (53%)

H5N1 Clinical Features

Source: The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian Influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85.

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Worldwide H5N1 Outbreak in Humans: 2003 - 2006

Source: WHO

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H5N1 Possible Travel Routes

• Legal poultry business

• Illegal bird trade

• Untreated fertilizer

• Migrating birds

• Humans (contaminated objects, intentional spread)

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H5N1 in Other Animals

H5N1 can infect other animals: – Pigs (China,

Vietnam)– Domestic cats; has

infected civet cats– Tigers, leopards

(Thailand, China)– Tiger-to-tiger

transmission (Thailand)

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In contrast to seasonal influenza, most H5N1 cases occur in previously healthy children and young adults.

Human H5N1 Epidemiology, Western Pacific Region

Source: WHO Regional Office for the Western Pacific

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• Primarily avian-to-human transmission

• No evidence of sustained person-to-person spread

• Limited probable person-to-person spread1

• Environment-to-human transmission possible

Human H5N1 Epidemiology

1 N Engl J Med 2005;352:333-340

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Influenza Pandemic Requirements

• A new Influenza subtype can infect humans

AND

• This new virus causes serious illness in humans

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• The new virus spreads easily from person-to-person

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Summary

• Influenza is a serious human and veterinary health concern each year

• Influenza virus strains evolve rapidly and can develop into a novel virus with pandemic potential

• Influenza pandemics have caused high morbidity and mortality in the past

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Summary

• H5N1 Avian Influenza is currently spreading through birds with occasional outbreaks among humans

• While there is evidence of rare human to human transmission, sustained transmission has not occurred

• If H5N1 virus obtains the ability to easily transmit from person to person, a pandemic may result

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Questions?

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Glossary VirusA small, infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell [a host] to reproduce.

Viral sheddingMultiplication of a virus in an infected person with subsequent release of the virus from that infected person, such that others who come into contact with the person may become infected. A state of being contagious.

EpidemiologyThe branch of medicine that deals with the study of the causes, distribution, and control of disease in populations.

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GlossarySeasonal InfluenzaExpected rise in influenza occurrence among humans living in temperate climates; occurs during the winter season with strains of influenza that have minor changes from season to season.

PandemicAn epidemic occurring over a wide geographic area and affecting a large proportion of the population.

Antigenic DriftA process of small changes in the genetic material of a virus, called point mutations, that occur during the normal virus replication process.

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Glossary

Antigenic ShiftA process of major changes in the genetic material of a virus; for influenza, the H and N proteins change altogether, resulting in a new strain of virus.

Highly Pathogenic Avian Influenza (HPAI)Influenza infection in poultry that causes severe illness and often death. Can be transmitted to humans resulting in severe illness or death.

Low Pathogenic Avian Influenza (LPAI)The most common influenza infection in birds; causes mild clinical and unapparent infections.

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References and Resources

• Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm

• The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian Influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85.

• Ungchusak K, et al. Probable Person-to-Person Transmission of Avian Influenza A (H5N1) N Engl J Med 2005;352:333-340.

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References and Resources

• Tiensin T, et al. Highly Pathogenic Avian Influenza H5N1, Thailand, 2004. EID;2005;11(11):1664-72. http://www.cdc.gov/ncidod/eid/vol11no11/05-0608.htm

• World Health Organization. Epidemic and Pandemic Alert and Response. 2006. http://www.who.int/csr/en/

• Center for Food Security and Public Health. Iowa State University: http://www.cfsph.iastate.edu/