Seasonal Influenza and Swine-Origin Influenza A (H1N1) Virus This presentation covers seasonal influenza and the novel swine-origin influenza virus (or S-OIV), with additional information about pandemics.

Part One Seasonal Influenza

Influenza Viruses Classified into types A, B, and C Types A and B cause significant disease worldwide Types B and C limited to humans Type A viruses More virulent Wild waterfowl reservoir Affect many species While there are three types of influenza viruses—A, B, and C—only two cause significant disease worldwide (A and B). Type B influenza viruses are limited to humans. Influenza type C infections cause a mild respiratory illness in humans and are not thought to cause epidemics. Influenza C viruses are not included in the influenza vaccine. Type A viruses, however, can cause severe disease in humans and affect many other species. Among the influenza viruses, Type A are considered to cause the most serious disease. Influenza A can cause severe epidemics as well as pandemics. The natural reservoir for Influenza type A is wild waterfowl, but it can infect multiple species including people, birds, pigs, cats, dogs, horses, and other animals. Wild waterfowl are the natural reservoir for influenza viruses. Influenza B viruses are usually found only in humans. Influenza B viruses can cause morbidity and mortality among humans, but in general are associated with less severe epidemics (more common among children) than influenza A viruses. Although influenza type B viruses can cause human epidemics, they do not cause pandemics. Photo: Cynthia Goldsmith, CDC 3 3

Influenza A Viruses Categorized by subtype Classified according to two surface proteins Hemagglutinin (HA) – 16 known subtypes Site of attachment to host cells Antibody to HA is protective Neuraminidase (NA) – 9 known subtypes Helps release virions from cells Antibody to NA can help modify disease severity 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, There are 16 known hemagglutinin subtypes for Influenza A. Each hemagglutinin subtype is named using an “H” plus a number, such as type H1, H2, and so on. Antibody against hemagglutinin is protective against infection. Neuraminidase is a surface protein that allows the virus to escape infected cells, and then go on to infect more cells. There are 9 known neuraminidase subtypes for Influenza A. Each neuraminidase subtype is named with an “N” plus a number, such as type N1, N2, and so on. Antibody against neuraminidase can modify or reduce the severity of an influenza infection. Because there are 16 HA and 9 NA proteins, there are 16 x 9 or 144 possible subtype combinations of the known HA and NA proteins. Hemagglutinin This image is in the public domain in the United States 4 4

Influenza A HA and NA Subtypes Other Animals Other Animals Other Animals Other Animals Other Animals Other Animals This figure illustrates the range of species that Influenza A sub-type viruses can infect. Some species that specific HA subtype viruses have infected are listed on the left, and some species that specific N1 subtype viruses have infected are listed on the right. The currently circulating strain is a novel H1N1 strain. 5 5

Seasonal Influenza Transmission Routes Influenza is an acute respiratory disease Signs and symptoms reflect respiratory route Fever, cough, headache, muscle aches Sometimes lower respiratory Transmission of influenza viruses Person-to-person through droplets from coughing or sneezing Transmission from objects (fomites) possible Infectious 1 day before and up to 7 days after becoming sick Human Influenza (commonly called “flu”) is an acute respiratory disease caused by infection with human influenza viruses. When asking ourselves “what does human/seasonal influenza clinically look like in humans” the first thing to consider is that influenza viruses typically attack the upper respiratory tract (upper airways) but can also sometimes infect the lungs. The clinical signs and symptoms of seasonal/human influenza reflect this. Influenza virus infection causes symptoms such as fever, cough, sore throat, headache, and muscle aches. If the virus has infected the lungs the typical symptoms of pneumonia such as fever and shortness of breath might be present. When we talk about surveillance and the ways that we might decide who should receive laboratory testing for influenza, these upper and lower respiratory symptoms will be apparent in the case definitions. Human influenza A and B viruses are thought to spread mainly from person to person on droplets generated by the coughing or sneezing of people with influenza. Sometimes people may become infected by touching something with flu viruses on it and then touching their mouth or nose (called fomite transmission). Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 days after becoming sick. That means that you may be able to pass on the flu to someone else before you know you are sick, as well as while you are sick. U.S. Centers for Disease Control and Prevention 6 6

Seasonal Influenza Communicability Viral shedding can begin 1 day before symptom onset Peak shedding first 3 days of illness Subsides usually by 5-7th day in adults Infants, children and the immunosuppressed may shed virus longer Infected persons can shed virus and possibly transmit human influenza from 1 day before they have symptoms to 5-7 days after the onset of symptoms. Peak viral shedding, or multiplication of the virus in an infected person during which the infected person can transmit viable virus to others, occurs during the 3rd day of illness. Infected persons are thought to be contagious for 4-5 days after the illness onset. However infants, children and immunosuppressed/immunocompromised patients (such as people with AIDS, or cancer patients on chemotherapy) may shed the influenza viruses in the upper respiratory tract and be infectious for longer periods of time. U.S. Centers for Disease Control and Prevention 7 7

Human Influenza Clinical Diagnosis Clinical symptoms non-specific Symptoms overlap with many pathogens Couple with laboratory data to verify diagnosis Even during peak seasonal influenza activity, only about 30% specimens tested for influenza are positive in the United States Clinical symptoms of human influenza are non-specific and overlap with many other respiratory disease caused by other pathogens. Thus, use of laboratory tests is helpful to verify a diagnosis of influenza. In the United States even during peak seasonal influenza activity, only about 30% specimens tested positive for influenza virus. This means that many other respiratory pathogens can produce clinical syndromes similar to that produced by human influenza virus infections. U.S. Centers for Disease Control and Prevention 8 8

Human Influenza Complications Sinus and ear infections Viral and bacterial pneumonia Myocarditis and Pericarditis Myositis Encephalopathy and encephalitis Febrile seizures Worsening of underlying chronic conditions Sepsis-like syndrome in infants Possible complications of human influenza include sinus or ear infections, viral and bacterial pneumonia, myocarditis, pericarditis, myositis, encephalopathy/encephalitis, febrile seizures and worsening of underlying chronic conditions. Infants may present with a sepsis-like syndrome. U.S. Centers for Disease Control and Prevention 9 9

Swine-Origin Influenza Virus (S-OIV) Part Two Swine-Origin Influenza Virus (S-OIV)

April 2009 Swine-Origin Influenza A (H1N1) Virus (S-OIV) The strain currently circulating is a novel Influenza A(H1N1) It is thought to be composed of avian, human, and swine components from various continents This strain is most likely a new subtype of A/H1N1 not previously seen in swine or humans The strains isolated in the US and Mexico appear to be identical In April 2009, health officials reported cases of a novel Influenza A H1N1 virus in Texas, California, and Mexico. The novel strain is thought to be composed of avian, human and swine components and has most likely not previously been seen in swine or humans. The strains isolated in the US and Mexico appear to be identical. This novel H1N1 strain is different than the seasonal H1N1 strain that circulated in the 2008-2009 influenza season.

General S-OIV Information There are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1 Swine-origin influenza viruses have high attack rates and low death rates in pigs Swine-origin influenza viruses do NOT typically infect humans – until this outbreak, there had been 12 cases in the US since December 2005, with no deaths 4 main subtypes of influenza A virus have been isolated in pigs; H1N1, the subtype currently circulating, H1N2, H3N2, and H3N1. In general swine-origin influenza viruses have high attack rates and low death rates in pigs. This means that many more pigs become sick than die from influenza. In addition, humans rarely become infected with swine influenza viruses. There were only 12 cases of swine influenza in humans from December 2005 until February 2009, with no deaths.

Food Safety You cannot contract swine-origin influenza from eating pork or pork products. Eating properly handled and cooked pork products is safe. Cooking pork to an internal temperature of 160°F kills the swine-origin influenza virus as it does other bacteria and viruses. You cannot contract S-OIV from eating pork or pork products. Cooking pork to 160°F kills the swine-origin influenza virus.

Transmission of S-OIV Human transmission of swine-origin influenza and seasonal influenza viruses is thought to occur in the same way Transmission can occur via: Contact with secretions from persons infected with swine influenza virus Contact with infected pigs or environments (surfaces, objects) contaminated with the virus Transmission of swine-origin influenza to humans can occur in two ways; contact with a person infected with the swine-origin influenza virus; and contact with infected pigs or environments, such as surfaces or objects, that have been contaminated with the virus. Human-to-human transmission of swine-origin influenza occurs the same way that seasonal influenza is transmitted from one person to another.

Human infection with S-OIV Symptoms may include: Fever, cough, headache, muscle aches (similar to seasonal influenza) Some people reported diarrhea, nausea and vomiting Symptom onset begins 1-5 days after exposure Infected individuals can spread the virus as long as they are symptomatic (or at least 7 days following illness onset)

Case Definitions Suspect Case: a person with acute febrile respiratory illness with onset within 7 days of close contact with a person who is a confirmed case of S-OIV infection, or within 7 days of travel to community either within the United States or internationally where there are one or more confirmed cases of S-OIV infection, or resides in a community where there are one or more confirmed cases of S-OIV infection. Probable Case: a person with an acute febrile respiratory illness who is positive for influenza A, but negative for H1 and H3 by influenza RT-PCR Confirmed Case: a person with an acute febrile respiratory illness with laboratory confirmed S-OIV infection at CDC by one or more of the following tests: real-time RT-PCR viral culture

Treatment of S-OIV The CDC recommends Oseltamivir (Tamiflu) and Zanamivir (Relenza) for treatment Oseltamivir is approved to treat and prevent infection in people at least 1 year old Zanamivir is approved to treat infection in people at least 7 years old, and to prevent infection in people at least 5 years old Antiviral drugs are most effective within 2 days of symptom onset There is currently NO vaccine available for swine influenza but it is anticipated that one will be developed in the next few months Because the virus is susceptible to Oseltaminir (Tamiflu) and Zanamivir (Relenza), the CDC recommends use of these antivirals for treatment. Conversely, the virus does not appear to be affected by amantadine and rimantadine. Antiviral drugs are most effective if taken within 2 days of symptom onset. There is currently no vaccine available for swine-origin influenza, but research and development of a new vaccine has begun and it is anticipated that a vaccine may be available in the Fall.

Part Three Pandemics

Requirements for an Influenza Pandemic Virus A new influenza A subtype virus emerges that can infect humans AND Causes serious illness Spreads easily from human-to-human in a sustained manner There are 3 requirements for an influenza A virus to cause a pandemic. First, it must be a new influenza A subtype that can infect humans. Second, it must cause illness, and third it must spread easily from human-to-human in a sustained manner. The key concept is sustained transmission. 19 19

Pandemic Influenza Phases The World Health Organization uses a 6-phase system to monitor pandemic progress. Phases 1 indicates no viruses circulating that could cause infection in humans. Phase 2 shows some virus circulation in animals only. Phase 3 shows infection in humans, but without sustained human-to-human transmission. Phase 4 indicates verified human-to-human transmission causing community-level outbreaks. Phase 5 denotes spread of the virus to at least two countries in one WHO region. Phase 5 indicates that a pandemic is imminent. Phase 6, or the Pandemic Phase, is characterized by community-level outbreaks in one additional country over the phase 5 criteria. Currently, the WHO has determined that the world is in Phase 5 with evidence of human-to-human transmission in Mexico and the United States.

Resources http://PandemicFlu.gov CDC’s Swine Flu Info Center: http://www.cdc.gov/swineflu/?s_cid=swineFlu_outbreak_001 WHO’s Swine Flu Info Center http://www.who.int/csr/disease/swineflu/en/