ABCs of Influenza and Pandemics

ABCs of Influenza and Pandemics
Module 2: ABCs of Influenza and Pandemics ABCs of Influenza and Pandemics Facilitator Notes: The purpose of this training module is to provide an academic introduction to seasonal and pandemic influenza. However, this presentation can be modified to meet other needs. For example, one could include slides on other respiratory diseases (e.g., SARS) that could figure in the differential diagnosis with the goal of improving surveillance and diagnosis of human infection with avian influenza. Rapid Response Team Training in Southeast Asia Photo: Cynthia Goldsmith

Module 2: ABCs of Influenza and Pandemics
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 Upon completion of this session, you will be able to: - Describe the characteristics of influenza infection in humans - Understand types of influenza viruses and how they can infect humans and animals - Describe the ways that influenza viruses can change or mutate

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 The learning objectives of this module are: - Contrast seasonal influenza outbreaks with pandemic influenza outbreaks - Understand the recent history of avian influenza outbreaks in humans - Describe the epidemiology and clinical characteristics of the current H5N1 outbreak in humans

Session Overview Influenza infection in humans Influenza virus Influenza epidemiology Avian influenza infection in humans To accomplish these learning objectives, we will begin by discussing some of the key characteristics of human infection with influenza viruses. We will then talk about the virus itself and its subtypes, the pattern of influenza disease in populations – or its epidemiology, and then we will specifically talk about the basics of avian influenza.

Influenza Infection in Humans
Module 2: ABCs of Influenza and Pandemics Influenza Infection in Humans We begin by asking “what is influenza” and “what does it look like” in humans (i.e., the key clinical characteristics of influenza infection in humans)

Key Characteristics Influenza is usually a respiratory infection Transmission Highly contagious Primarily through contact with respiratory droplets Transmission from objects possible - Influenza (commonly called “flu”) is a respiratory infection – the virus attacks the respiratory tract (upper airways and lungs) so it causes symptoms such as cough or sore throat - The influenza virus is very contagious and can easily spread from person to person - Human influenza is a respiratory infection that is spread through direct contact with respiratory secretions from an infected person who is sneezing and/or coughing - Indirect transmission from objects (such as contact with contaminated surfaces or clothing) is also a possible means of transmission

Key Characteristics Communicability Transmission days before to 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 Infected persons can transmit influenza anywhere from 1-2 days before they have symptoms to 4-5 days after the onset of symptoms. This means that the person is contagious, or sheds virus, for 3 to 5 days. Peak viral shedding (when infected persons are most likely to infect others) is on day 1 of symptoms. Infants, children and immunocompromised patients (such as people with HIV, or cancer patients on chemotherapy) can transmit the virus for longer periods of time.

Key Characteristics 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 The incubation period, the time period from exposure to the onset of symptoms, for influenza is fairly short, between 1 and 5 days. The short incubation period makes influenza outbreaks difficult to control. Human Influenza usually peaks in winter months (which are December – March in the Northern Hemisphere and May – September in the Southern Hemisphere) within temperate zones but occurs year-round in tropical zones.

Typical Signs and Symptoms
Module 2: ABCs of Influenza and Pandemics Typical Signs and Symptoms Rapid onset of symptoms Fever / Chills Body aches Sore throat Non-productive cough Runny nose Headache The hallmark of influenza is the sudden, rapid onset of symptoms. Influenza symptoms may include fever, chills, body aches, sore throat, non-productive cough, runny nose and headache.

Groups at Risk for Serious Complications
Module 2: ABCs of Influenza and Pandemics 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 Complications of Influenza infection include pneumonia, dehydration, or worsening of chronic lung and heart problems, and even death. Groups at high risk for influenza complications are: - Persons 65 and older - Persons with other chronic medical conditions, such as lung or heart disease, or diabetes - Infants between the ages of 6 months and 2 years - Pregnant women - Nursing home residents - Children on long-term aspirin therapy

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 - The influenza vaccine is the main way of preventing influenza infection and its serious complications - Each year, 3 inactivated viruses are selected for the vaccine based on information about circulating strains. (Usually, the vaccine includes 2 type A strains and 1 type B strain). Therefore, the vaccine can only protect us from the 3 influenza subtypes selected for inclusion in the vaccine and will provide no protection for any new pandemic subtype resulting from antigenic shift. (More will be discussed about influenza subtypes and the phenomenon of antigenic drift/shift later in this presentation) - The vaccine is distributed prior to the influenza season in countries within the temperate zone, and is administered through a shot, or injection, to those in high risk groups who are 6 months of age or older - An intranasal spray vaccine is also available but its supply is limited

Influenza Virus Now, we briefly discuss the influenza virus itself and its unique ability to change its structure to evade the body’s immune system.

Influenza Virus Types A and B
Module 2: ABCs of Influenza and Pandemics Influenza Virus Types 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 While there are three types of influenza viruses—A, B, and C—only two cause significant disease in humans (A and B). Type B influenza viruses are limited to humans, whereas Type A viruses can cause severe disease in humans and affect more species. Influenza Type A Type A influenza is considered to cause the most serious disease among the influenza viruses, although not all strains cause clinical disease. Influenza A can cause severe epidemics (as well as severe worldwide epidemics; or pandemics) among all ages. Influenza type A infects multiple species including people, birds, pigs, horses, and other animals. Wild birds are the natural hosts for these viruses. Influenza Type B Influenza B viruses are usually found only in humans. Influenza B viruses can cause some morbidity and mortality among humans, but in general are associated with less severe epidemics (chiefly among children) than influenza A viruses. Although influenza type B viruses can cause human epidemics, they have not caused pandemics. Because avian influenza and all pandemic viruses are of the Type A variety, we will focus this session on Type A influenza viruses.

Influenza A Virus Subtyping
Module 2: ABCs of Influenza and Pandemics Influenza A Virus Subtyping Influenza A subtypes are determined by two surface glycoproteins Hemagglutinin (HA) Neuraminidase (NA) 16 HA’s and 9 NA’s Influenza A viruses are further subtyped by two proteins on the viral surface, called hemagglutinin (or HA) and neuraminidase (or NA). Hemagglutinin allows the virus to attach to host cells, while neuraminidase allows the virus to escape infected cells, and then go on to infect more cells. There are 16 known hemagglutinin and 9 known neuraminidase subtypes for Influenza A. Each hemagglutinin subtype is named using an “H” plus a number, such as type H1, H2, and so on. In the same way, each neruaminidase subtype is named with an “N” plus a number, such as type N1, N2, and so on. Many different combinations of HA and NA proteins are possible.

Species Infected by Influenza A, HA and NA Subtypes N1 H1 N2 H2 N3 H3 H4 N4 H5 N5 H6 N6 H7 N7 H8 N8 H9 N9 This figure illustrates the range of species that Influenza A sub-types can infect. The species that specific HA subtypes can infect are listed on the left, and the species that specific N1 subtypes can infect are listed on the right. Note that wild migratory waterfowl can be infected with all subtypes. Within the H5 and H7 subtypes, certain strains can be severe. H10 H11 H12 H13 H14 H15,16

Surface Protein Changes
Module 2: ABCs of Influenza and Pandemics 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 The Influenza virus undergoes mutations, or changes, frequently, so the virus is constantly changing. There are two main ways for these changes to occur: Antigenic DRIFT and Antigenic SHIFT. Antigenic DRIFT results in a minor change to the shape of the virus surface proteins. Antigenic DRIFT is a process of small changes, called point mutations, that occur during the normal virus replication process. Antigenic DRIFT changes do not change the virus subtype. Antigenic drift does change the virus just enough that people do not have complete immunity to it after the changes occur. However, some people may have partial immunity to the changed virus resulting from antigenic drift and experience less severe clinical disease from infection with that virus. This allows influenza viruses to change slightly and re-infect people repeatedly. It is the reason why virus strains in the vaccine must be updated each year. Much more rarely, the H and N proteins change altogether. When this major change occurs it is called antigenic SHIFT and it results in the introduction of a new influenza subtype. If this new influenza subtype has the ability to cause disease in humans, it can result in a worldwide influenza epidemic (pandemic). Antigenic shift can occur in two possible ways: In the first, influenza A viruses of two different subtypes simultaneously infect the same host, allowing “reassortment,” or exchange of viral RNA segments in the host’s cells, resulting in a virus that contains genes from both subtypes. For example, pigs have been considered effective “mixing vessels” because they contain receptors for both avian and human viruses. Pigs may be infected by human and avian influenza A viruses at the same time, and a new “reassorted” virus may emerge that contains genetic material from both original viruses. (note: humans may also act as mixing vessels) If such a virus were to infect people and spread easily, the human population would be completely susceptible and therefore unprotected against the new subtype. This mechanism likely created the viruses that were responsible for the pandemics of 1957 (H2N2) and 1968 (H3N2). The second possible mechanism for antigenic shift is direct transmission of influenza virus from birds or other animal species to humans, the virus then evolves to adapt to the new human host. Direct infections of humans with avian influenza viruses of A subtypes have occurred in the past decade (such as the recent infections associated with H5N1), but no sustained human-to-human transmission of avian influenza A viruses has occurred. There is also strong evidence that the 1918 pandemic resulted from direct transmission of influenza virus from avian species.

Re-assortment and Direct Transmission DIRECT Non-human virus Human virus - This illustration demonstrates the concept of antigenic shift through the two mechanisms described in the previous slide: genetic re-assortment and direct transmission - Pigs can be infected by avian (bird), swine (pig), and human Influenza A viruses. They therefore can serve as mixing vessels for genetic re-assortment. If a pig was to be infected by both a bird and human influenza A virus, re-assortment of gene segments could occur resulting in a novel, hybrid influenza virus, part avian and part human. The resulting virus strain is referred to as a “reassortant” virus. - Alternatively, an avian virus can directly transmit to humans and through adaptation become a human virus Reassortant virus

Influenza Epidemiology
Module 2: ABCs of Influenza and Pandemics Influenza Epidemiology Now we will focus on influenza epidemiology – that is, the populations and types of people that influenza affects.

Epidemiology Terms Endemic A disease that occurs at an expected constant level in a population “Background” level First, let’s cover some terms. The word “Endemic” refers to a disease that occurs at an expected or constant level in a population. Sometimes endemic occurrence of a disease is called the background level or rate of disease. Note that diseases that occur in seasonal or yearly spikes can still be considered endemic, if the seasonal increase in occurrence is expected. This graph shows monthly mortality from pneumonia and influenza in Canada. The red line shows the expected number of deaths. The line goes up and down as the expected number of deaths increases each winter and decreases each summer, showing an expected seasonal pattern. Red line: Expected deaths each year Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet] Apr. Available from

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 An epidemic occurs when the cases of a disease exceed what is normally expected. Shown here is the same graph of influenza in Canada as the previous slide. The black line on the graph shows the actual number of influenza deaths that occurred each year. On the far left, we see that there was an epidemic of influenza in Canada in 1951, because there is a large increase in the number of cases that occurred in Canada. A pandemic is an epidemic that occurs over a large geographic area, or across the whole world. The increase of cases noted in 1957 and in 1968, which are circled on the graph, were due to pandemics. There was an increase in cases not only in Canada in these years, but across the whole world.

Impact of Seasonal Influenza
Module 2: ABCs of Influenza and Pandemics Impact of Seasonal Influenza An annual public health problem Substantial health impact % 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) Influenza rapidly spreads around the world in seasonal epidemics and causes an annual public health problem. Seasonal influenza affects about 10 to 35% of children and 5 to 20% of adults living in temperate climates every year. Seasonal influenza also has a large economic impact because infected adults and children must miss work and school. There are many related healthcare costs and medical care systems may be overwhelmed. Finally, there is growing evidence that tropical zones also suffer a great burden, both in the health of citizens and economic losses, due to annual influenza outbreaks.

Seasonal Epidemics vs. Pandemics 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 While seasonal influenza occurs every year, pandemic influenza rarely occurs. Here we compare some features of seasonal influenza with features of pandemic influenza. While the population usually has some immunity built up from previous exposures to seasonal influenza, the human population lacks any immunity to pandemic influenza strains. In seasonal influenza epidemics, infants and the elderly are most at risk of illness and complications. But during an influenza pandemic, even healthy, young people are at increased risk for serious complications. Seasonal influenza strains are the result of Antigenic Drift, while pandemic influenza strains are the result of Antigenic Shift.

Mortality Impact of Past Pandemics Spanish Flu (H1N1) ~ 40 million deaths worldwide Asian Flu (H2N2) 1 - 2 million deaths worldwide Hong Kong Flu (H3N2) ~ 700,000 deaths worldwide Previous pandemics have caused a great number of deaths worldwide. The pandemic, often referred to as the Spanish Flu , was an H1N1 strain. It caused approximately 40 million deaths worldwide. The pandemic, or Asian Flu, was an H2N2 strain and caused about 1-2 million deaths worldwide. And in , the Hong Kong Flu, an H3N2 strain, caused about 700,000 deaths worldwide.

Timeline of Influenza Pandemics H9 Avian Influenza H7 H5 H3 H2 H1 This diagram shows the three pandemics from the last century on a timeline. It has been over 37 years since the last pandemic in 1968, but Avian influenza strains threaten to cause the next pandemic because they can cause serious disease in humans and humans lack any immunity to these strains. However, these strains have not acquired the ability to transmit human to human yet. 1957 Asian Influenza H2N2 1968 Hong Kong Influenza H3N2 1918 Spanish Influenza H1N1

WHO Stages of a Pandemic
Module 2: ABCs of Influenza and Pandemics WHO Stages of a Pandemic Inter-pandemic period Pandemic alert period Pandemic period Post pandemic period The World Health Organization (WHO) has published a global influenza preparedness plan. This plan outlines the phases of an influenza pandemic and specifies the role of the WHO, identifies public health goals and makes recommendations for national measures before and during a pandemic. Specific recommendations can be made depending on the progress of the epidemic. For this reason, WHO has defined the stages of a pandemic. They are: the Inter-pandemic period the Pandemic alert period the Pandemic period the Post-pandemic period You should be familiar with these, so we will talk about each phase.

WHO Phases of a Pandemic
Module 2: ABCs of Influenza and Pandemics 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 The first two phases of a pandemic are considered part of the Inter-pandemic period. - In phase 1, there is no new Influenza subtype causing illness in humans and the risk of illness with a new influenza subtype is low - In phase 2, there are still no new virus subtypes, but animal subtypes pose a risk of human disease The distinction between phase 1 and phase 2 is based on the risk of human infection or disease resulting from circulating strains in animals.

Module 2: ABCs of Influenza and Pandemics WHO Phases of a Pandemic 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 The next step up is the Pandemic Alert period. During this stage a new (meaning new to humans) influenza virus subtype is causing human illness. In phase 3, there are no verified instances of human to human spread (humans are a “dead end” host for the virus). In phase 4, there are instances of human to human spread, but clusters are small and they are highly localized. At this phase the virus is not well adapted to humans. In phase 5, the clusters of ill persons are larger, indicating that the virus is adapting itself to humans. At this phase, there is a high risk for a pandemic to occur. The distinction between phase 3, phase 4, and phase 5 is based on an assessment of the risk of a pandemic. The world is currently in phase 3 (although scientists are debating whether there is sufficient evidence that human-to-human transmission has occurred in local outbreaks, therefore making a phase 4 designation more appropriate).

Module 2: ABCs of Influenza and Pandemics WHO Phases of a Pandemic Pandemic Period Phase 6: Increased and sustained transmission in the general population. Post Pandemic Period Recovery phase In the pandemic period (phase 6), the virus has adapted to humans and can transmit easily from person to person. Pandemics often occur in a series of waves of 8-12 weeks. For example, the 1918 pandemic had a mild wave in the Spring of 1918 followed by a deadly wave in the Summer of 1918. The post pandemic period is the recovery phase when the virus has exhausted susceptible persons and the next inter-pandemic period begins again.

Avian Influenza Next we will specifically discuss the biology, clinical features, and epidemiology of human infection with avian influenza.

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 Currently, scientists believe that a pandemic strain of influenza is most likely to develop from an avian Influenza type A virus, such as the H5N1 strain that is currently circulating in birds through much of the world. Avian Influenza A viruses differ from human Influenza A viruses in several respects: - All type A viruses can infect birds and many do infect birds without causing any disease - However, certain subtypes (H5N1 and H7N7) are deadly to many species of birds—especially domestic poultry - Infected birds excrete large amounts of virus in respiratory secretions, saliva, and feces. Avian viruses may be transmitted to humans and other animals through contact with respiratory secretions and feces. These viruses may survive at low temperatures, at low humidity, and in water for days to weeks. Other modes of transmission including contamination of clothing, farm equipment, water, and feed are possible.

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 Avian influenza viruses are further classified into one of two categories based on their genetic features and/or their ability to cause severe disease. Low pathogenic AI (LPAI) is most common influenza infection in birds. It generally causes mild clinical (e.g., decreased food consumption, respiratory signs) disease. LPAI strains may be any subtype (H1 to H15) but highly pathogenic AI (HPAI) are generally H5 or H7 subtypes. HPAI causes severe illness in poultry and often death. Mild LPAI H5 or H7 subtypes can mutate into HPAI H5 or H7 subtypes

Avian Influenza in Humans
Module 2: ABCs of Influenza and Pandemics Avian Influenza in Humans Year Subtype Location Cases Deaths 1996 H7N7 United Kingdom 1 1997 H5N1 Hong Kong 18 6 1998 H9N2 China 1999 2 2002 H7N2 United States 2003 The Netherlands 89 2004 H7N3 Canada Worldwide 228 130 In recent years, there have been several outbreaks of Avian Influenza among humans. The largest ongoing outbreak is caused by the H5N1 influenza virus. This outbreak began in Southeast Asia in 2003, but has recently spread to countries outside of that region (e.g., Egypt, Turkey, Iraq, Azerbaijan). In total (as of 22 June 2006), 228 human cases have been reported from 9 countries and 130 persons have died from H5N1 infection.

H5N1 Clinical Features Incubation period likely 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 The incubation period for H5N1, or the amount of time between exposure to the virus and onset of symptoms, may be longer than for seasonal Influenza. For H5N1, it is generally in the range of 2 days at the lower limit to as many as 8 days at the upper limit. Rarely, there have been case-to-case intervals in household clusters of 8-17 days, possibly due to unrecognized exposure to infected animals or environmental sources. The initial symptoms of Avian Influenza are generally respiratory and include cough, sore throat, and runny nose accompanied by a high fever. Unlike seasonal Influenza, frequent watery diarrhea is sometimes observed with H5N1 infection. Abdominal pain and vomiting are also sometimes observed. 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 Sep 29;353(13):

H5N1 Clinical Features Clinical course Shortness of breath (Dyspnea) Clinical pneumonia with variable x-ray findings Acute Respiratory Distress Syndrome (ARDS) Case Fatality Rate (53%) Shortness of breath occurs an average of 5 days after onset of illness. This usually progresses into clinical pneumonia, and changes in the lungs can be observed by x-ray. Acute respiratory distress syndrome can also develop. The case fatality rate is currently about 50 percent. Death has occurred predominately among infants and children, and an average of 9 to 10 days after illness onset. The cause of death is due to progressive respiratory failure. One caveat is that these observations may be affected by surveillance biases. 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 Sep 29;353(13):

Worldwide H5N1 Outbreak in Humans: 2003 - 2006
Module 2: ABCs of Influenza and Pandemics Worldwide H5N1 Outbreak in Humans: This map shows nations with confirmed cases of H5N1 Avian influenza in humans (in red). As of 22 June 2006, there have been ten countries with confirmed cases of H5N1 in humans. These countries are Vietnam, Indonesia, Thailand, Cambodia, China, Turkey, Iraq, Egypt, Azerbaijan and Djibouti. Source: WHO

H5N1 Possible Travel Routes
Module 2: ABCs of Influenza and Pandemics H5N1 Possible Travel Routes Legal poultry business Illegal bird trade Untreated fertilizer Migrating birds Humans (contaminated objects, intentional spread) There are many suggested theories for how the H5N1 virus can spread throughout the world. Both the legal and the illegal poultry trade may contribute to the spread of H5N1 by the movement of poultry and other birds sick with H5N1 across borders. The widespread use of untreated poultry feces as a fertilizer is another possible risk factor. Migrating birds also appear to be a means of virus spread since ducks and other migratory fowl can be infected without illness. Humans may also play a direct role in the movement of H5N1, either through contamination on clothes or farm equipment or through purposeful contamination such as bioterrorism or agricultural terrorism.

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) H5N1 influenza can also infect other animals. Pigs have been infected in China and Vietnam, and that’s a concern since pigs could serve as a mixing vessel for re-assortment of Avian and human Influenza virus strains. This leads to the possibility of a newly created virus being able to infect humans. Transmission of H5N1 to both domestic and wild cats (tigers, leopards) has been demonstrated as well.

Human H5N1 Epidemiology, Western Pacific Region In contrast to seasonal influenza, most H5N1 cases occur in previously healthy children and young adults. This graph shows human infection with Avian Influenza as of February, 2006, in countries of the Western Pacific Region. The bars from left to right represent age groups, from children ages 0-9 years on the left, through adults aged 79 years on the right. The different colors on the bars represent different countries. Most human cases of H5N1 have occurred among young adults and children, which is very different from seasonal Influenza. Note the drop in the number of cases in persons older than 40 years. Source: WHO Regional Office for the Western Pacific

Human H5N1 Epidemiology Primarily avian-to-human transmission No evidence of sustained person-to-person spread Limited probable person-to-person spread1 Environment-to-human transmission possible Contact with sick poultry, or avian-to-human transmission, still remains the major risk factor for human H5N1 influenza. Among the recent cases, most patients had direct contact with sick or dead poultry. Plucking and preparation of ill birds, handling fighting cocks, playing with poultry—especially asymptomatic infected ducks; and consumption of duck’s blood or possibly undercooked poultry have all been associated with transmitting the virus from birds to people. No cases have acquired H5N1 from eating cooked poultry. Sustained person-to-person spread has not occurred. However, there have been a few instances of limited person-to-person transmission. In one documented case of human-to-human transmission, H5N1 probably spread from a girl to her mother and aunt. Other cases of probable transmission between family members have also recently occurred. H5N1 can survive in the environment, and can be present in water sources that birds visit. Human intake of contaminated water by swimming or drinking, or getting contaminated water in the eyes are possible routes of transmission from the environment to humans. (N Engl J Med 2005;352: ) 1 N Engl J Med 2005;352:

Influenza Pandemic Requirements
Module 2: ABCs of Influenza and Pandemics Influenza Pandemic Requirements A new Influenza subtype can infect humans AND This new virus causes serious illness in humans The new virus spreads easily from person-to-person To tie this information back with the WHO phases of a pandemic, it is important to note that the H5N1 outbreak has met 2 of the 3 requirements for a pandemic thus far: it is a new influenza A subtype that can infect humans, and the virus causes serious illness. As long as human and bird infections continue, there are opportunities for the virus to obtain the 3rd requirement of human transmissibility.

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 Seasonal influenza is a serious human and veterinary health concern each year. The influenza virus strains have the ability to evolve rapidly and can develop into a novel virus with pandemic potential. At several times in the past 100 years, influenza pandemics have occurred and caused high morbidity and mortality.

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 H5N1 Avian influenza is present in wild and domestic birds in more and more countries, with occasional outbreaks among humans resulting in a very high death rate. Currently there is evidence of rare human to human transmission, but sustained transmission has not occurred; the virus is not readily transmitted from one person to the next. Humans become infected primarily by having contact with infected birds. However, if this virus were to change by antigenic drift or antigenic shift, it could obtain the ability to easily spread from person to person. If this happens, it could be the beginning of the next worldwide pandemic. For this reason, we must carefully monitor strains of avian influenza, detect any changes in the virus, track human cases, and respond to outbreaks as quickly as possible.

Questions?

Glossary Virus A 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 shedding Multiplication 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. Epidemiology The branch of medicine that deals with the study of the causes, distribution, and control of disease in populations.

Glossary Seasonal Influenza Expected 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. Pandemic An epidemic occurring over a wide geographic area and affecting a large proportion of the population. Antigenic Drift A process of small changes in the genetic material of a virus, called point mutations, that occur during the normal virus replication process.

Glossary Antigenic Shift A 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.

References and Resources
Module 2: ABCs of Influenza and Pandemics References and Resources Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet] Apr. Available from 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 Sep 29;353(13): Ungchusak K, et al. Probable Person-to-Person Transmission of Avian Influenza A (H5N1) N Engl J Med 2005;352:

References and Resources
Module 2: ABCs of Influenza and Pandemics References and Resources Tiensin T, et al. Highly Pathogenic Avian Influenza H5N1, Thailand, EID;2005;11(11): World Health Organization. Epidemic and Pandemic Alert and Response Center for Food Security and Public Health. Iowa State University:

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