Influenza. By Allison Canestaro-Garcia. Disease Etiology:

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1 Influenza By Allison Canestaro-Garcia Disease Etiology: The flu is an infectious disease caused by a subset of viruses of the family Orthomyxoviridae. There are 7 different viruses in this family, four of which are different species of Influenza virus [1]. This includes Influenza A virus, Influenza B virus, Influenza C virus, and Influenza D virus. Influenza D only infects animals so it is not currently a concern for humans. Influenza A, B, and C, on the other hand, all infect humans. Influenza C is the least common, only infects humans, and presents the most mild symptoms. Similarly, influenza B only infects humans, but it is more common, and presents more severe symptoms [2]. Unlike either type B or C, influenza A is present in both animals and humans, it is the most common, and presents the most severe symptoms [6]. It is beautifully designed to infect us and evade our bodies defences. Disease Transmission: The most common way for influenza A to spread is by droplet transmission from one infected human to another. The virus can travel up to 6 feet when you talk, cough, or sneeze [4.] It is possible to spread the disease even before you present any symptoms [9]. Another way the virus spreads is through contaminated surfaces. For example, if an infected person sneezes into their hands then touches a doorknob, they leave the virus behind. Influenza is able to survive up to 24 hours on surfaces [5]. The least common way to contract influenza is by direct contact

2 with infected animals, also by means of droplet transmission [6]. For example, people with extensive exposure to pigs can become infected with influenza A H3N2v [9]. Reservoirs: With influenza A, both humans and animals can act as reservoirs. Infected humans are the most common reservoir that we encounter [9]. Yet many animals (birds, dogs, bats, horses..etc) also carry versions of influenza that can spread to humans [6,7,8,9]. When we began to see influenza A (H3N2) spread from pigs to humans we labeled these cases as variant and denoted them with a lowercase v to distinguish them [6]. Although the influenza A (H3N2)v that infects pigs and the influenza A (H3N2) that infects humans are of the same subtype, they are distinct [7]. Cases of this virus spreading from pigs to humans in the US has been limited and cases of humans spreading to other humans are quite rare [6,7]. Pigs present a worrisome scenario as there is great potential for them to act as mixing vessels for reassortment of subtypes across species [8, 9]. Specific Microbial Characteristics: Influenza A is an enveloped negative-strand RNA virus with a genome made up of 8 RNA segments [1]. This segmented genome plays an important role in antigenic shift, one of the viruses virulence factors [10]. Influenza A can be further subdivided by the surface antigens hemagglutinin (H) and neuraminidase (N). Hemagglutinin initiates infection by binding to the surface of our cells and neuraminidase is essential to releasing the virus from infected cells [10,11]. These antigens stud the surface of the envelope and can vary somewhat in their structure [2]. There are currently 18 different types of hemagglutinin (H1-H18) and 11 different types of neuraminidase (N1-N11) identified. The two most common subtypes to infect humans are H1N1 and H3N2 [6]. These subtypes also infect various animals [9]. Specific Tests for Identification: There are currently more 10 different rapid influenza diagnostic tests (RIDT) approved by the FDA [12,13]. These tests all detect viral antigens in specimen acquired from the upper respiratory tract of patients. Results are generally available in about mins [12]. Some can differentiate between influenza A and B while others cannot. Some use an analyzer reader device, for example an immunoassay, to standardize the interpretation of results while others do not [13]. Quite a few of them can work with different types of specimen but each is approved by the FDA for only certain types. These tests are not as sensitive (50-70%) or specific

3 (90-95%) as viral culturing or reverse transcription polymerase chain reactions. On the other hand though, they are quick, easy, and cheap [12,13]. Signs and Symptoms: The incubation period for influenza is very short, generally lasting only 1 to 4 days and averaging about 2 [14]. As mentioned earlier, you are able to transmit the disease about 1 day before symptoms start. Influenza is characterized by a rapid onset of illness. Signs include high fever, cough, sneezing and symptoms include malaise, headaches, general aches and pains [5,12]. The infection generally passes in about 3-10 days for most healthy people but it can cause more severe symptoms and even death [14]. Respiratory illness such as pneumonia can develop either as a primary influenza viral pneumonia or a secondary bacterial pneumonia infection. Certain person are at increased risk for more severe disease including the very young, very old, pregnant women, immunocompromised person, and people with certain chronic health condition [1]. Over the last three decades, it is estimated between 3,000-49,000 people died each year from complications from the flu [15]. This is a pretty wide range which points to the fact that there are a number of factors at play here. Historical Information: There are varying opinions as to when the first epidemic of influenza took place [1,16,17]. Most sources agree that the Spanish Flu is the worst recorded pandemic. An estimated 50 million people died worldwide with around 675,000 deaths in the United States alone [1]. Pandemics come to pass when a influenza strain humans have not experienced, like one that infects birds or pigs, crosses over to infect us. It is believed that the Spanish Flu originated from birds, an influenza A H1N1 subtype [6]. As humans have no immunity to these new viruses, large proportions of the population become infected and thus many die. One of the unique features of this pandemic is that it killed many healthy and relatively young people aged [17]. With this epidemic in mind, scientists went to work to first isolate the virus and make a vaccine. It was not until 1933, while experimenting with some ferrets, scientist finally isolated the virus and thus were able to make the first monovalent vaccine in 1936 [18,19]. Virulence Factors: The influenza vaccine is constantly being updated because of both antigenic drift and antigenic shift. The influenza virus is highly mutagenic due to the fact that its RNA polymerase does not have a proofreading mechanism. This leads to point mutations[1]. Antigenic drift is happening all the time, slowly, and gradually changing the virus. These changes can give a virus a

4 competitive advantage over the old version of virus. Say for example, preventing antibodies from binding to it. Antigenic drift gives rise to closely related viruses and can lead to epidemics as previous immunity is no longer fully effective [1,18]. Antigenic shift on the other hand is the cause of pandemics. This is a the sudden emergence of a new subtype of influenza A likely due to the genetic recombination between viruses present in humans and animals [18]. How this works is that a host cell in an animal, a pig for example, has two closely related viruses in it. One that normally infects pigs and one that normally infects humans. With both viruses present in the cell they are able to ressort their segmented genomes, giving a new virus [1,18]! This can present as a new hemagglutinin or a new neuraminidase or even both. As humans have never seen this antigen before we have no antibodies for it so the infection can spread quickly, thus leading to pandemics. [6,16]. Control/Treatment: Treatment for most people is pretty basic. One should stay home, get some rest, and drink plenty of fluids [5]. There are antiviral drugs available that can shorten the length of your illness. These drugs work best when taken 1 to 2 days after your symptoms begin but they can still help outside that window [20]. Prevention/Vaccines: Since 1971 the World Health Organization (WHO) began giving formal recommendations as to what should go into the seasonal flu vaccine based on information gathered by the Global Influenza Surveillance Network (GISN). In 1998 they switched from giving a recommendation once a year to twice a year as the southern and northern hemispheres experience influenza season at different times [22]. This allows for more information gathering and modifications to be made as needed. These are just recommendations, each country still has the ability to choose what actually goes into their own particular vaccine [21]. Today the GISN processes somewhere between 150, ,000 infected respiratory samples attributed to 5000 viruses annually. It takes months to develop and put into production vaccines at such a large scale so recommendations come out about 8 months in advance [22]. The flu vaccine is made of 3 or 4 of the influenza viruses that research supports being most prevalent [22]. The vaccine can come in many forms but traditionally the vaccine is an inactivated virus made using an egg-based manufacturing process [21]. There is also a liveattenuated virus made this way but this year it is no longer being recommended [24]. Vaccine are also being made in mammalian cells and by using recombinant technology [23].

5 Local Cases/Outbreaks: Influenza is endemic in the US with the highest number of cases cropping up between October and May. The CDC starts counting cases on the first of October. As of this week there are 7,178 confirmed cases of influenza with just over 74% of those being type A [25]. In Texas, as of December 2nd there are 1399 confirmed cases of influenza with 1017 of those cases being type A [26]. Global Cases/Outbreaks: In addition to the Spanish Flu pandemic, there are 3 other pandemics that are noteworthy. The first is the pandemic of 1957 was caused by influenza A (H2N2) which originated in East Asia. This pandemic was named the Asian Flu and resulted in 66,000 deaths in the US. In 1968 the world faced subtype influenza A H3N2. This pandemic does not have a particular name but it resulted in the deaths of more than 100,000 Americas. Most recently, a new strain of influenza A (H1N1) began circulating The CDC estimates over 60 million people became infected with this flu but only about 12,500 death were attributed to it in the US. Ninety percent of hospitalizations and deaths, unlike normal seasonal influenza outbreaks, occured in people younger than 65 years of age. This H1N1 subtype along with the 1968 H3N2 subtype are still circulating today and the most dominant types of flu we see annually. Yet none of these pandemics came close to causing as much death as the Spanish Flu did [18]. References: 1. Taubenberger, Jeffrey K. and Morens, David M. The Pathology of Influenza Virus Infections National Center for Biotechnology Information. U.S. National Library of Medicine, National Institute of Health, 28 Feb Web. 8 Dec Types of Influenza Viruses. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 27 Sept Web. 8 Dec A revision of the system of nomenclature for influenza viruses: a WHO Memorandum. World Health Organization. U.S. National Library of Medicine, National Institute of Health, Web. 7 Dec How the flu spreads. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 5 Oct Web. 7 Dec

6 5. Flu: Overview. National Health Service. United Kingdom Department of Health, 4 Jan Web. 8 Dec Influenza virus infections in humans. World Health Organization. World Health Organization, Feb Web. 7 Dec cines/influenza_virus_infections_humans_feb14.pdf?ua=1 7. Situation Summary on Influenza A (H3N2) Variant Viruses ( H3N2v ). Center for Disease Control and Prevention. Office of the Associate Director for Communication, 3 Aug Web. 9 Dec Parrish, Colin, et al. Influenza Virus Reservoirs and Intermediate Hosts: Dogs, Horses, and New Possibilities for Influenza Virus Exposure of Humans. Journal of Virology. American Society of Microbiology, 24 Dec Web. 9 Dec Transmission of Influenza Viruses from Animals to People. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 12 Apr Web. 9 Dec Bouvier, Nicole M. and Palese, Peter. The biology of influenza viruses. National Center for Biotechnology Information. U.S. National Library of Medicine, National Institute of Health, 12 Sept Web. 9 Dec Matrosovich, Makhai N., et al. Neuraminidase Is Important for the Initiation of Influenza Virus Infection in Human Airway Epithelium. National Center for Biotechnology Information. U.S. National Library of Medicine, National Institute of Health, Nov Web. 9 Dec Diagnosing Flu. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 3 Oct Web. 9 Dec Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 26 Oct Web. 9 Dec Clinical Signs and Symptoms of Influenza. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 26 May Web. 8 Dec Estimating Seasonal Influenza-Associated Deaths in the United States. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 9 Dec Web. 10 Dec Rinsho, Nihon. History of influenza epidemics and discovery of influenza virus. National Center for Biotechnology Information. U.S. National Library of Medicine, National

7 Institute of Health, Oct Web. 9 Dec Past Pandemics. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 2 Nov Web. 10 Dec Immunology and Vaccine-Preventable Diseases. Center for Disease Control and Prevention. Office of the Associate Director for Communication, No Date. Web. 10 Dec Hannoun, Claude. The Evolving History of Influenza Viruses and Influenza Vaccines. Medscape. WebMD, Dec Web. 11 Dec What you should know about flu antiviral drugs. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 5 Jan Web. 7 Dec Selecting Viruses for the Seasonal Influenza Vaccine. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 4 May Web. 8 Dec A Description of the Process of Seasonal and H5N1 Influenza Vaccine Virus Selection and Development. World Health Organization. World Health Organization, 19 Nov Web. 9 Dec How Influenza (Flu) Vaccines Are Made. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 7 Nov Web. 9 Dec Quadrivalent Influenza Vaccine. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 3 Oct Web. 10 Dec Weekly U.S. Influenza Surveillance Report. Center for Disease Control and Prevention. Office of the Associate Director for Communication, 8 Dec Web. 9 Dec Texas Influenza Surveillance Activity Report. Texas Health and Human Services. Texas Department of State Health Services. 2 Dec Web. 9 Dec Influenza-Surveillance-Activity-Report.xls