Wednesday, March 20, 2013

Influenza


This week at Infection Landscapes we will cover influenza, one of the most significant respiratory diseases to affect humans, and which does so on an annual basis. Influenza causes substantial morbidity and mortality each year in both the developing and developed world.

The name "influenza" is derived from the Italian word for influence because, centuries ago, it was believed that this disease occurred as a result of the influence of the movement of the sun and the stars given its seasonal nature.

The Pathogen. Influenza is caused by one of three genera of influenza viruses in the Orthomyxoviridae family: influenza A, influenza B, and influenza C. Of these three, influenza A is the most virulent and thus is responsible for the greatest burden of disease. As such, most of this discussion will focus on influenza A.


Influenza A viruses are enveloped and have an RNA genome in 8 segments. The genome is single stranded and negative sense, and is enclosed in a helical capsid:


Hemagglutinin (HA) and neuraminidase (NA) are important surface glycoproteins that facilitate virion entry into and exit from the host cell. As such, these surface structures are key features of virus infectivity and pathogenicity. HA functions as the attachment glycoprotein to the cellular receptor, sialic acid, on columnar epithelial cells of the respiratory tract. Thus, HA specificity for receptor binding is a determinant of which species can be infected, i.e. the host range, which will be discussed in more detail later. Specific antibodies to HA epitopes prevent attachment and entry of the influenza virus particle into the host cells, and are thus an important aspect of immune protection against infection. NA cleaves sialic acid residues to allow virus particle release from the host epithelial cell. It is suspected that specific anti-NA antibodies diminish the release of new virions from host cells, thus curtailing an infection. The infection cycle of the virus in the host cell is very nicely depicted in the graph below published by Influenza Report:


The animated video below also provides a nice depiction of the infectivity, pathogenicity, and immunogenicity of influenza A. 



Antigenic variation is very important to influenza A evolution, particularly as this relates to the annual epidemics and multidecadal pandemics experienced by humans. Before talking more specifically about these two phenomena, it will be helpful to highlight two features of the molecular biology of the virus that are particularly important to its rate of genetic change. First, the genome is comprised of RNA molecules. Many such RNA viruses, including influenza A, exhibit low fidelity and, thus, a high rate of mutation because they lack the proofreading provided by DNA polymerase, which is a necessary enzyme for DNA virus assembly. Second, the genome of influenza A virus is segmented, which further contributes to the high rate of genomic change because the genes encoded on particular segments of one genome can more easily be exchanged with segments of other influenza A genomes from multiple virus particles that happen to infect the same host cell.

There are two fundamental evolutionary genetic processes at play in the antigenic properties of influenza A virus. The first is antigenic drift. Antigenic drift defines the minor yet frequent genetic changes in the HA and NA surface antigens that occur on an annual or near-annual basis. Antigenic drift leads to approximately 1% change in the HA antigen per year. This rate of mutation is the leading force driving the annual epidemics experienced every year around the world during the regular influenza season. However, there is a second, equally important, process involved. The second is antigenic shift. Major changes in the amino acid composition for the HA or NA surface antigens, or both, can lead to a new viral subtype. These new subtypes will present (in most instances) to a completely immunologically naive population wherein everyone, or nearly everyone, is susceptible to infection. It is believed that after several decades (typically between 10 and 30 years) of circulation of a specific influenza A subtype, most members of the population will have antibody to that subtype. This accumulated population immunity places selective pressure on the virus and leads to new shift variants that emerge by way of reassortment. The new subtypes lead to pandemic influenza events.


The patterns of transmission during the annual epidemics that correspond to antigenic drift, and the multidecadal pandemics that correspond to antigenic shift will be described later in the epidemiology section.

The Disease. Clinical disease typically presents with abrupt onset of fever and respiratory symptoms, including cough, rhinorrhea and sore throat. Malaise and prostration are very common. Myalgia and headache are more common with influenza than with other respiratory infections. In addition, gastrointestinal symptoms are not common in adults, but 50% of infant and child infections may have vomiting, abdominal pain and diarrhea. However, none of these symptoms are definitive for influenza infection. Only cell culture demonstrating influenza A virus can distinguish influenza from other agents causing respiratory infection, such as a rhinovirus (a frequent source of the "common cold"). Nevertheless, influenza infection is on average associated with more severe disease than the pathogens responsible for the common cold. Symptomatic disease usually lasts 3 to 5 days, but complications can prolong the illness.


The complications associated with influenza make the infection particularly dangerous, especially for infants, the elderly, and individuals who are immunocompromised. Some individuals can develop primary viral pneumonia, which frequently can be fatal. However, primary viral pneumonia is not very common. Secondary bacterial pneumonia is much more common, particularly among the susceptible groups mentioned above, and can occur up to two weeks after the acute viral infection. In infants and children, otitis media and croup are common complications. Myocarditis, myositis and encephalitis are less frequent complications.

The Epidemiology and the Landscape. Influenza A virus is spread via droplet, airborne and contact transmission, with droplet transmission probably serving as the most important during seasonal transmission. The overall attack rate in large populations is typically between 10% to 20% during the annual epidemics (seasonal flu), however some subpopulations or local outbreaks can have attack rates approaching 40%. These higher attack rates usually occur in children and, as such, they play a critical role in the spread of influenza in communities during the annual epidemics. Indeed, schools and/or daycare centers will often serve as the primary loci of infection transmission during these epidemics. This is reflected in the typical peak incidence of infection occurring in young school age children prior to the peak in any other age group. The annual global incidence of influenza is unknown given the extreme difficulty in recording and classifying respiratory infections that do not result in hospitalization in most parts of the world. However, the annual global mortality attributable to influenza is estimated to be between 250,000 and 500,000 deaths. In the United States, the annual incidence is estimated to be between 35 and 50 million cases, with between 200,000 and 250,000 hospitalizations and 36,000 deaths.

The prevalence of influenza in a single simulation of the United States 100 days after the start of an influenza epidemic with R0=1.6. The color of each dot corresponds to the illness prevalence in a census tract.

The above map (published in PLoS Comput Biol 6(1): e1000656. doi:10.1371/journal.pcbi.1000656) simulates the typical distribution of prevalent influenza cases in the US once the seasonal epidemic has begun, given that each infectious case will, on average, lead to more than one new infectious case in a completely susceptible population (R0=1.6). The map demonstrates the high level of transmission, as well as the potential need for the mobilization of resources, in urban areas.

Seasonal, or epidemic, influenza follows a annual, roughly predictable, pattern each year in the temperate regions of the northern and southern hemispheres. In the southern hemisphere, epidemics usually occur in the May to September winter season, while in the northern hemisphere they occur from October to May. For example, in China, Europe, and North America, the epidemic peak(s) usually occurs between November and March: manifested first by high rates of school and industrial absenteeism, followed by an increase in visits to health care facilities, an increase in pneumonia and influenza hospital admissions, and finally an increase in deaths from pneumonia or influenza. In any specific locality, epidemic influenza often begins abruptly, reaches a peak within three weeks, and usually ends by 8 weeks. A given region can also experience 2 epidemic peaks with different virus strains, either in sequence or with overlap. In tropical climates influenza can occur in seasonal epidemics, often during the monsoon or rainy seasons, or endemic transmission can occur throughout the year. The former tropical pattern may suggest that, in these areas of high humidity, powerful climatic forces such as a monsoon may cause people to spend more time indoors in close proximity to each other and thus facilitate spread of disease. Regardless of the time of year, geography, or climate, epidemic influenza occurs because of antigenic drift, i.e. the slow incremental changes that accrue in the viral genome by way of mutation as described above.

Pandemic influenza does not occur in a regular predictable pattern each year, but rather occurs only periodically over the course of decades and can be much more severe because all or a large proportion of the the population is immunologically naive and clinically susceptible to the new emerging virus. These are the antigenic shift events, i.e. widespread global infection following those changes in the viral genome that are due to reassortment. Over the course of the last one hundred years, 5 such shift events have occurred that have lead to 5 subsequent pandemics. The most devastating of these was the 1918 shift to the H1N1 subtype, which resulted in the death of approximately 50 million people worldwide. In 1957, influenza A shifted from the H1N1 to the H2N2 subtype, but with a much lower global burden of disease than the previous 1918 pandemic. In 1968, influenza A H2N2 was replaced by influenza A H3N2, which circulated for the next decade until, in 1977, the influenza A H1N1 subtype re-emerged. This re-emergence was associated with very high attack rates (~50%) in individuals born after 1956 as they had not been exposed because the H1N1 subtype had been replaced by the H2N2 subtype in 1957. For the next three decades, from 1977 until 2009, the re-emerged H1N1 and H3N2 subtypes co-circulated in the population causing the annual influenza epidemics each year. Then, in 2009, a new influenza A H1N1 subtype emerged in Mexico and subsequently replaced the earlier H1N1 subtype. This most recent pandemic in 2009 did not cause the extensive morbidity and mortality that was feared at the beginning of the outbreaks in North America. Overall, morbidity and mortality were lower than in previous pandemics. It is believed that this may have been due in part to the reduced morbidity and mortality among people over the age of 65 years. Nevertheless, there was substantive morbidity and mortality associated with this pandemic and it followed atypical patterns. For example, the vast majority of deaths (~96%) occurred in people under the age of 65, whereas the majority of deaths (~90%) occur in people over the age of 65 during seasonal influenza epidemics. Moreover, the number of deaths due to influenza in children was 4 times greater during the 2009 pandemic than what it is during seasonal influenza epidemics.

It is important to discuss the ecologic relationship between human epidemic influenza and pandemic influenza. To begin, there are strains of influenza A virus that infect humans, there are strains that infect birds, and there are strains that infect pigs. Nevertheless, all influenza A viruses circulating today are evolutionarily derived from bird influenza A. Birds, and in particular waterfowl, are the natural primary reservoir host for all current circulating bird inlfuenza A. These birds are also, either directly or indirectly via another intermediate host (generally pigs), the historic reservoir for all influenza A that subsequently adapted to other animals. New subtypes of human influenza A typically emerge when the genome of a current circulating human influenza A subtype reassorts with the genome of a subtype of current circulating bird influenza A or the genome of a subtype of current circulating pig influenza A. Pigs can harbor infection with several influenza subtypes because they have the epithelial cell receptors for both bird and human HA. As such, pigs are considered important "mixing vessel" hosts for reassortment events. However, in order for a new human subtype to become a pandemic virus it must 1) be new to a relatively large proportion of the population; i.e. the global population must be relatively immunologically naive to the new subtype, 2) it must be able to replicate and cause disease in humans, and 3) it must be easily transmissible between humans. The last point is particularly important as the new subtype will not become a human inlfuenza A subtype if it cannot be transmitted between people, even if human infection is possible zoonotically. Infection with the highly pathogenic avian influenza A H5N1 (commonly referred to as bird flu) exemplifies this. This is a bird inlfuenza A subtype, not a human inlfuenza A subtype. While this bird subtype is capable of infecting and causing severe disease in some humans, it is not currently capable of causing a pandemic because it cannot be transmitted efficiently from person to person. The graphic below produced by the National Institute of Allergy and Infectious Diseases nicely depicts the species and transmission pathways that can lead to antigenic shift in the influenza A virus and subsequent pandemics.


The mixing of different influenza A subtypes from different animal species is central to producing new and potentially dangerous subtypes that can result in new human influenza A, which can subsequently lead to new pandemics. Moreover, the nature of such genetic exchange makes the elimination of human influenza A virtually impossible. There are two primary landscapes that converge to optimize reassortment of influenza A subtypes: 1) the sylvan landscapes and migratory paths of waterfowl and, 2) the agricultural lands and markets, both subsistence and industrial, of humans. The spaces where these converge are places where sylvan birds can come into contact with domestic birds (e.g. chickens), which may also be in direct contact with pigs. As such, these landscapes can be important sources of diverse influenza A subtype circulation among multiple hosts and may serve as important sources of human exposure.


Control and Prevention. There are four important tactics that have demonstrated effectiveness in either preventing infection or mitigating the effects of an active infection. The first is very simple: regular hand washing during the flu season. This certainly need not be obsessive, but the regular practice of washing your hands with regular bar soap (NOT antibacterial soaps or hand sanitizers, which can be harmful to our microbiome) after returning home from populated public spaces during flu season makes good sense. The second is even more simple, though rarely followed: stay home when sick. The likelihood of transmitting influenza virus to susceptible people is quite high during illness. In addition, given that influenza virus is typically more virulent than many of the respiratory pathogens associated with the common cold, an infected individual requires significant rest to convalesce. As such, going in to work or school during a respiratory illness can be dangerous both to oneself and one's peers. Third, the use of antiviral drugs can be used to reduce the duration of symptoms among infected individuals and may help prevent transmission to their susceptible contacts. There are two classes of these drugs: the neuraminidase inhibitors, oseltamivir and zanamivir, and the M2 inhibitors, amantadine and rimantadine. The neuraminidase inhibitors block the release of new virions from the surface of infected host cells. The M2 inhibitors block the release of viral RNA into the host cell after the virion has entered the cell. The fourth important measure of control and prevention is vaccination.

The previous discussion of antigenic drift highlighted the importance of influenza virus mutability. This requires that a new vaccine is produced each year because the vaccines stimulate an immune response that targets those same components of HA and NA antigens whose genes are subject to the high rate of mutation. The process of having to renew vaccine production with new strains of virus on an annual basis has made achieving a consistently high level of vaccine effectiveness difficult. Nevertheless, it is currently the best we have and the vaccine effectiveness is not negligible.

There are two types of vaccine: an inactivated vaccine (the injection) and a "live" attenuated vaccine (nasal spray). Neither of these vaccines are capable of causing influenza. The overall vaccine effectiveness for the inactivated vaccine against seasonal influenza based on recent meta-analyses is approximately 60% (the "live" vaccine seems to have a higher effectiveness, however the data are much more limited because so much less of the this vaccine is produced). While this is certainly not ideal, it still does provide a level of protection that can have some important implications. First, specific subpopulations, such as school children, can be very important for targeted vaccination as these are typically the loci of epidemic transmission and community dissemination of seasonal influenza. Moreover, there is evidence that the vaccine effectiveness is markedly better in children. Blocking transmission in this setting, even with imperfect effectiveness, can have important implications for the epidemic curves of localized outbreaks, as well as the national incidence of severe illness and hospitalizations and deaths. Second, the vaccine, even when it does not prevent infection for a given individual, can still mitigate the severity of that infection. As such, the people who are vaccinated and do get infected still benefit from protection because they will generally experience illness that is less severe than those who were not vaccinated. And, as discussed above, the problem with influenza is the potential for developing complications when illness is severe. Third, there are subgroups in the population who are at particularly high risk for influenza infection. These are infants and small children, the elderly, and immunocompromised people. By getting vaccinated, we significantly reduce the risk of transmitting what could be a deadly infection to these high risk people by either preventing the infection in ourselves, or by limiting the severity of disease we experience if we do get infected and thus our transmissibility to others. If you are wondering whether or not the influenza vaccine is for you just read through the infographic below by TeleVox:

Do I Need A Flu Vaccination?

One caveat is that both inactivated and live attenuated vaccines use chicken eggs in their production and so both would be contraindicated for anyone with severe allergies to egg proteins. This caveat should soon be eliminated, however, as the US Food and Drug Administration has just recently approved the first cell-cultured vaccine.

41 comments:

  1. Wow very nice post this post helpfull for me.
    Yeast is a type of fungus; when one speaks of a yeast infection this is referring to the fungus scientifically
    known as Candida. The specific type of fungus most commonly responsible for vaginitis is Candida albicans.
    Yeast infection no more review
    Yeast is commonly present on normal human skin and in areas of moisture, such as the mouth and vagina.
    In fact, it is estimated that between 20% to 50% of healthy women normally carry yeast in the vaginal area.

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  2. I was interested by the description of how the mortality distribution of the 2009 H1N1 epidemic differed from previous influenza epidemics. I understand that children are often affected by seasonal influenza, but I wonder why the children were more likely to die than older individuals in 2009. Did older individuals not get infected in the first place, did they respond better to treatment, or did they get more/better treatment?

    I'm also interested in the antiviral medications. Why aren't they more commonly used? Is there a fear that the virus will develop a resistance to the drugs?

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    1. I suppose due to lack of immunity and higher incidence of complications named above like viral pneumonia and superadded bacterial infections, mortality was higher in children.
      Antiviral are useful only if used early in the course of disease and are effective in reducing the natural course of disease. Maybe by the time a patient feels awful and shows up at doctor’s office, the window period from maximum drug benefit already passes. Also all these drugs have numerous side effects, so physician would tend to avoid use unless indicated.
      Due to its antigenic properties, virus can develop resistance to drugs. H1N1 was supposedly resistant to Oseltamivir.

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    2. Some further explanations on the previous comment:
      The 2009 H1N1 viruses are susceptible to neuraminidase inhibitor type of antiviral drugs, oseltamivir and zanamivir. CDC recommends the use of antiviral medications for prevention be limited to certain circumstances. Use of oseltamivir or zanamivir for prevention should only be considered for people at higher risk for influenza complications, or persons who work in health care settings or provide emergency medical care. Don't start antiviral drugs to prevent illness if more than 48 hours have passed since the exposure.

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    3. From the New H1N1 strain it seems children were higher at risk since H1N1 was a major cause of death in 1918, and thus people who were born before the mid 1950s were most likely exposed to this form of the flu. Which in turn serves as the elderly population in 2009. Secondly children are relatively inept with hygiene thus making them biological Peachtree dishes. The effective contact rate for children is usually much higher in most infectious diseases and thus the disease is spread easier, with that being said it is not that uncanny children were the main targets of the 2009 H1N1 epidemic.

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    4. During my undergraduate years in college I worked in the infection control department of a community hospital in New Orleans organizing data on patients who contracted H1N1. Something important that was notated in the database was whether or not the patient had illnesses associated with the respiratory system, cardiac system, diabetes, obesity and overall all who were immuno-compromised. Stephen, I know you discuss how children and the eldery are more likely to develop H1N1 and I also think it is very important to look at those populations who are already experiencing other illnesses as high risk groups.

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  3. I find the antigenic properties of the influenza A virus to be very fascinating.

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  4. @ Allison- I think the older population may have developed immunity from previous exposure that was similar to the new H1N1, so they were able to produce some antibodies to the new H1NI. Thus, reducing their morality rate.

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    1. Further explanations on the previous comments:
      12,000 deaths have resulted as a consequence of the 2009 H1N1 flu. The number of child deaths (aged 17 and under) is estimated to be around 1250. The highest hospitalization rates have occurred in younger populations, with the highest hospitalization rate reported in children 0-4 years old.. It seems H1N1 virus gives a more severe damage to the lung system in children than elder or it is more infectious to children or the treatment is more effective on elder than young people. Research is still looking for the mechanism of the H1N1 virus to know more about its cause of disease.

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    2. @patricia, from what I understand the older population was not immune to this new H1N1 because it replaced the previous re-emerged form from the 1970s. The post states that this H1N1 followed atypical patterns; morbidity and mortality were not seen in adults 65+ not because of previous exposure but because it was atypical. I do wonder if this strain of H1N1 had similar components that did make for a stronger immune response in older adults. Also, because strains of infuenza A have the ability to re-emerge, do we store vaccines from previous outbreaks in case of re-emergence?

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  5. Nicole MastrogiovanniJuly 8, 2014 at 10:56 PM

    Influenza is tricky because the strain is constantly changing every year or even every season. It is important for individuals, especially those working in schools, daycares, hospitals, doctors offices, or with the elderly, to be vaccinated every year. I enjoy that there is now a nose spray for influenza because a lot of people and children are afraid of shots and by offering another option, maybe more citizens would be willing to have the spray who used to not be protected due to a fear of injection. However, as great as vaccinations are, I think we must as public health professionals really push on with washing your hands advice, again especially to children in school. Influenza can be infectious and spread from droplets, airborne, and contact so if we can knock out one of those options (contact) just by washing hands whenever they are around sick people, out in public, or even just every time they enter their home, I think it would cut down on a lot of people falling ill and also spreading the flu to family members and friends.

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    1. Nicole, 

      Great point about hand advice.

      Hygiene routines are very important that some may neglect. Simple hand washing and covering the mouth when sneezing or coughing are preventative measures which help reduce transmission. Vaccines are also a great way to protect ourselves, however due to the consistent change of influenza, vaccines have to be changed. Many people have stopped getting vaccinated due to personal beliefs and therefore prevent their kids from vaccinating. Some believe in the herd immunity but that is not as reliable as before. As Public Health professionals, the first step should be educating the public about the importance of hygiene and vaccinations. 

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  6. I found it quite interesting that latest 2009 H1N1 sub-type atypically targeted the young and seemingly spared most folks over the age of 65. As we know, the elderly are generally among those at highest risk for complications from influenza; yet in 2009, we disproportionately saw the greatest morbidity/mortality in the young. If we think back to the pandemonium in 2009, we recall that many of us ended up getting 2 different flu vaccines that year. That was because the "regular" seasonal flu vaccine had been developed and distributed well before we understood that we were in the mist of a pandemic involving a novel strain of the newly emerged H1N1.

    In any event, the theory was that although no one could have possibly developed antibodies against this particular H1N1 strain (it was new), cross-reactive antibodies from other similar stains may have offered older individuals some protection. In fact, a study done later that year showed that while children had no cross-reactive antibody reaction to the new strain, 6-9% of adults ages 18 to 60 had it, and 33% of even older adults had it. This suggests that the immune memory of prior exposure to similar stains may have boosted the immunity of our elderly against the 2009 H1N1 sub-type.

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    1. I think there are several interesting points in the post. The description about antigenic drift and antigenic shift provides me with new insight on the occurrence of influenza outbreak. How these concepts are related to annual flu epidemics and multidecadal pandemics are something that I never thought of before. At that same time, I remember that you told us in EPID5311 that the abuse of antibiotics has facilitated the emergence of some novel diseases. Therefore, I am just wondering if the use of antiviral drugs to treat influenza has also contributed (partly) to the slow but ongoing process of mutation in these viruses. Another thing I find interesting is that although vaccination is not always effective, it can help reduce the severity of influenza if one ever has it. Honestly, I did not know about that. I remember that when I was working in a cardiovascular clinic, I often heard elderly patients complain about the effectiveness of flu vaccine (that they still had the flu after vaccination) and how futile it was. As a public health student, I think it is necessary to inform the public (especially the elderly) that vaccination does help protect our health even though it cannot complete prevent us from getting infected.

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  7. (Sorry for posting it twice because I posted in the wrong place. Please delete the previous post.)

    I think there are several interesting points in the post. The description about antigenic drift and antigenic shift provides me with new insight on the occurrence of influenza outbreak. How these concepts are related to annual flu epidemics and multidecadal pandemics are something that I never thought of before. At that same time, I remember that you told us in EPID5311 that the abuse of antibiotics has facilitated the emergence of some novel diseases. Therefore, I am just wondering if the use of antiviral drugs to treat influenza has also contributed (partly) to the slow but ongoing process of mutation in these viruses. Another thing I find interesting is that although vaccination is not always effective, it can help reduce the severity of influenza if one ever has it. Honestly, I did not know about that. I remember that when I was working in a cardiovascular clinic, I often heard elderly patients complain about the effectiveness of flu vaccine (that they still had the flu after vaccination) and how futile it was. As a public health student, I think it is necessary to inform the public (especially the elderly) that vaccination does help protect our health even though it cannot complete prevent us from getting infected.

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    1. I agree with Pui Ying in that too many people abuse antibiotics. They go to see the doctor for mild afflictions and get antibiotics for things that will get better on their own and in the same time. This is allowing viruses to mutate as well as weaken the patients immune system. Working as a Respiratory therapist in a hospital setting I came across parents who would claim that the flu vaccine would make their children sick and that they would avoid giving the vaccine to their younger children in the future. This is why I agree that it is important for the field of public health to focus on bringing increased awareness to communities bout the flu vaccines benefits and how it works.

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  8. I found it very interesting that the 2009 H1N1 strain cause 4 times as many deaths in children as seasonal flu strains. I can remember being in School for respiratory therapy and being introduced to H1N1 by our professors. They as well as the whole medical community were in a panic. Thankfully it was not as bad as they expected. It's a good thing that they are making a flu vaccine that does not use egg protein because I myself knew of a few healthcare workers who could not take the vaccine due to their allergies and had issues being allowed to go to work and see patients. I would also like to say that I found picture # 7 very informative in how a flu virus can be transferred from animal to human and back to animal when the human is infected with 2 flu strains allowing it to mutate, then go back to human.

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    1. Hi David,
      I agree with you about picture #7: what a great image to help understand the transmission of this virus with which we have all had some sort of experience. I also really liked the video posted here, which Dr. Walsh showed in class (I watched it again here because it really helped me understand what was going on with actual infection with influenza.
      Regarding HA and NA mutations as they relate to transmission between humans and animals, you may like the CDC's page about influenza transmission: http://www.cdc.gov/flu/about/viruses/transmission.htm#subtypes. The diagram at the bottom of the page is a pretty good reference, if you're interested.
      Ben

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  9. As we are approaching flu season, the public service announcements and advertisements promoting influenza vaccination are increasing. Influenza is a disease eligible for vaccination because it can be easily diagnosed and, as mentioned above, has a predictable season. Vaccination is extremely important during flu season but many healthy people refuse to get vaccinated because they either believe they will get the flu from the vaccine or they believe that they're healthy enough to fight the flu. As we read, neither flu vaccine on the market can cause the flu and the vaccine not only protects healthy individuals, but also the children, the elderly, the immunocompromised and others for which vaccination isn't an option.

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    1. I was intrigued to find out recently that the New York City's MTA has started making announcements about covering ones mouth and nose when sneezing or to stay home if one has an elevated fever. I think such public health announcements are important and noteworthy especially in times when other flu like symptoms are on rise.

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    2. I also found it interesting during this flu season how MTA buses use announcements telling passengers how to prevent the spread of flu by proper covering techniques or just staying home. Its definitely a good idea to put these announcements in public transportation since that is where a lot of transmitting can occur. I also think it would be beneficial to include advertisements with images showing the ways to cover oneself if coughing or sneezing ( since a majority of people do not take advantage of using their elbow) or other ways to protect yourself such as proper hand washing techniques as well. It would be useful for visual learners as well as elderly, foreigners, or children who may not be able to hear or understand the announcements very well.

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    3. It's equally important to note that you're at higher risk when you're on the subway! Dirty poles and seats, coughing and sneezing everywhere. I've seen in other countries where hand sanitizers have been placed throughout public transportation facilities to combat the spread. Additionally subway advertising should include the myth buster that the flu shot makes you ill. This is critical to getting more people vaccinated.

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  10. I received my inactivated influenza vaccination today. Vaccination is extremely important for particular subgroups in the population. Infants, children and the elderly are highly vulnerable to influenza virus and suffer from greater severity of symptoms. There are two FDA approved injectable forms of the influenza vaccine; inactivated influenza vaccine and the recombinant influenza vaccine known as Flublok. Inactivated influenza vaccine contains egg products. Individuals with egg-allergy, who are administered the egg-containing influenza vaccine often suffer a severe anaphylaxis reaction and death. Flublok contains hemagglutnin protein from three strains of the influenza virus. The recombinant form does not contain any Avidin or egg product (therefore can be administered in individuals with Avidin allergy) and is not a live vaccine (can be administed to immunocompromised patient).

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    1. Hi Hari,
      I think it was good to explain the available vaccines for influenza and how they work ad for whom they should be given. Also it would be great to inform the public that vaccination does not cause influenza in-itself, and if someone took the vaccine and then got flu-like symptoms and signs that does not mean they had the flu or that the vaccine caused the symptoms/signs they had. since we are in the season for flu and flu-like infections, I wonder how it would be possible to differentiate between them and the Ebola symptoms and signs especially when there is a potential outbreak.

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  11. I have found influenza information very interesting and informative. Before reading information about influenza I could not believe that influenza viruses are able to mutate and because of their genetic mutations there are different influenza vaccines each year. I found two interesting facts about seasonal influenza vaccinations. The first interesting fact is that vaccinating pregnant women reduces their infants hospitalization by 92 percent and it is also proven to protect their babies up to six months after their birth. The second interesting fact is that seasonal influenza vaccination reduces cardiac events among people who have heart problems.

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    1. Thank you for that point about cardiac events, Kataryna. Every year I inevitably end up "discussing" with my aunt the importance of the flu vaccine is, yet she always refers to that "one time she got the shot and got sick from it." Even though I try explaining to her that she most likely already "sick" with another type of pathogen, she is still very hesitant to receive the vaccine.

      Now I can prevent her with the fact that vaccination was associated with lower rates of some cardiac events among people with heart disease, especially among those who had had a cardiac event in the past year -- since she herself has heart problems.

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  12. I find it interesting that it was initially believed that the movement of the sun and stars made influenza occur. I also found it interesting that it is said that in between 10 and 30 years, most will have the antibodies involved with influenza A. When the "bird flu" was discussed, I did not know that the was rare that this strain can cause illness in humans and that it would never be able to cause a pandemic. I remember when the bird flu was all over the media. The misinformation being portrayed to the public made it seem as though this strain of the flu was capable of pandemic proportions. I also love the chart at the bottom depicting whether or not to get a flu shot.

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    1. I know exactly what you mean about the misinformation often portrayed in the media, Stacy. It was informative to read that the bird subtype of flu that is "capable of infecting and causing severe disease in some humans, is not currently capable of causing a pandemic because it cannot be transmitted efficiently from person to person.'

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    2. As Stacy expressed, there are many interesting facts about the ecology of the influenza virus. It is amazing that it is the combination of hosts that keeps the antigenic shift alive, which was well depicted in the graphic on this blog. An annual epidemic known to contribute to 40,000 US deaths annually definitely puts the virus into a perspective that I have never appreciated before. For me, the missing link in the ecology is the period of time after the epidemic has resolved; after the human host has fought off the flu, via vaccine or with their own immune system; where does the event of the mutation of the virus occur if the host is no longer immunologically naive. Does the annual re-emergence of the human flu necessitate interaction with other hosts? Where is the epicenter of the replicating influenza virus? If this is knowable, could it lead to lead to ecological prevention efforts?

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  13. One of the things that the blog speaks about indirectly, is the huge miss conception most people have which is the notion that the common cold (which is mainly cause by the influenza virus) can be "caught" by prolonged exposure to cold weather such as rain or winter conditions. But base on the information provided we realize that the viruses that cause the common colds regardless of the time of year, geography, or climate, epidemic influenza occurs because of antigenic drift, the slow incremental changes that accrue in the viral genome by way of mutation.

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    1. I assume that you mean the annual epidemics of influenza are due to antigenic drift? It's interesting that you bring up the connection between the common cold and influenza. Having a case of the flu can also make one susceptible to contracting a cold virus. This may add to the confusion between the common and cold and the flu since a person can have both viruses at the same time. It would be interesting to consider how antigenic drift of influenza may influence antigenic drift of the common cold. Because the flu may make one more susceptible to cold viruses (e.g. immunogenic response to common cold may be compromised due to the immune system still trying to deal with the flu), does the flu aid in the antigenic drift of cold viruses?

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  14. S.Wallace--There is no doubt that the influenza vaccine is a good prevention method. However, it does bug me that the chemistry of the vaccine every year is pretty much based on prediction. A prediction that failed last influenza season where there was a lot of talk of the 2014-2015 flu vaccine being widely ineffective. Of course, there is hope in the field one day for a universal flu vaccine that would address all strains and I think that would be the most effective form of prevention. However, it seems like a hefty task to pursue which I hope can be accomplished one day. Although the burden of disease is not as great in the U.S. or similar to other diseases, I was still quite shocked with regard to how many people are hospitalized and die in the United States in this day and age.

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  15. This entry states that compared to other respiratory infections the most common symptom for influenza is myalgia and headache. It is also mentioned that gastrointestinal symptoms are not common in adults but common in infants. I am interested in knowing the anatomy and specific details behind why myalgia and headache are common symptoms and why children get gastrointestinal symptoms but adults do not. I am also interested in the knowing more about the statement that the movement of the sun and the stars, depending on the season, was believed to have influenced influenza. Lastly, I learned that many RNA viruses exhibiting low fidelity and a high rate of mutation virus assembly and the genome of RNA virus being segmented contributes to the high rate of genetic change. This was helpful to understand the molecular biology of the virus.

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  16. http://www.nytimes.com/2009/05/25/world/middleeast/25oink.html?

    On May 2 2009 Egypt slaughtered 300,000 pig as a proactive measure in the swine flu scare. It was the only country in the world to order a mass pig slaughter in response to the disease despite no swine flu cases reported in the country! The move mirrored Egypt's battle with bird flu, in which the government killed 25 million birds within weeks in 2006....

    I don't know how to describe this other than how a weak government worrying that public fear over the disease may lead to it's fall. Not that this helped as it was toppled anyway by the 2011 revolution.

    The lesson thou is how politics greatly influence public health; in this case, a knee jerk reaction that has no effect on stopping an epidemic (that thankfully never materialized), causing the loss of livelihood of thousands of poor people and the loss of a food source in a country that can't afford either....

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  17. Influenza is a viral disease that humans have had to battle over the years because of its unique genetic makeup and the way that the viruses can mutate and become (re)infectious. Because of the potential harms the virus can cause, the government is keen on taking precautionary steps to prevent its spread before anything disastrous happens. One thing the government does right is the community level outreach for influenza vaccine vaccination every year. Over the years, access to these vaccines have also improved. In addition, as a response to outbreaks from earlier years, states have required health workers to receive influenza vaccines (or wear a mask) during contact with patients.

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    1. The point that healthcare workers must receive the flu vaccine is a good point, Liz. Since the virus succumbs to both antigenic drift and shift (with the former being an important factor in the annual outbreaks), it is necessary that these workers receive the vaccine when around a vulnerable population (i.e. those in the hospital).

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  18. "Pandemic influenza does not occur in a regular predictable pattern each year, but rather occurs only periodically over the course of decades and can be much more severe because all or a large proportion of the population is immunologically naive and clinically susceptible to the new emerging virus. "

    A not on this: The CDC currently publishes weekly influenza reports to track the disease and note for any outbreaks. However, going back a few years, they didn’t publish a report until they had collected data from across the country and were certain of an outbreak. This took several weeks to a month to happen and by that time the "flu season" was already well underway. Interestingly enough, Google created something called Google flu trends. Utilizing the questions people were searching they graphed out the increase in search for flu like symptoms. This helped predict the flue epidemic while it was happening. Many epidemiologists refuted Google’s Flu Trends because it was not based off actual influenza infections being reported. Google has since stopped this program and the CDC now issues weekly reports on the flu epidemic.

    Link to Google Flu Trends: https://www.google.org/flutrends/about/

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    1. It seems like a good outcome for the CDC to produce more timely data but for Google not to publish data that could be misleading and a course for panic. This week the CDC has published data showing that the hospitalization rate for flu is twice as high in high poverty census tracts than inflow poverty census tracts. They only suggest reasons for this but likely some combination of low access to vaccination, overcrowded housing and poorer overall health which is exacerbated by flu infections. It is a good reminder about how viruses cause infections in humans but how the disease plays out can be determined by human factors.

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    2. I found the CDC weekly reports very interesting - I did not realize how much information was collected and available for the public!
      I was unable to find data about associations to poverty census tract for this week. Nevertheless, I found Edith's thoughts on the causes of disparity to be wise. Also, I did find that nearly 92% of adult hospitalizations for flu were in patients with at least one underlying medical condition. (http://www.cdc.gov/flu/weekly/index.htm#S6)
      In addition, I looked at the FluView map on the website (http://gis.cdc.gov/grasp/fluview/main.html). The states with the highest ILI and flu activity were predominantly in the southeastern US, which makes me even more curious about the question I asked in class: do regional differences in humidity affect a population's susceptibility to respiratory infections?

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  19. I always knew that influenza strains changed from year to year, and the vaccine had to be adjusted accordingly, and ahead of time. However, now that I have a better understanding of antigenic drift and antigenic shift, I can see how difficult this process could be. It was mentioned that the 2009 H1N1 epidemic was not as deathly as expected, perhaps due to improved outcomes for people over 65. I wonder if the atypical pattern could have been due to improved or better-than-expected vaccine development and strain prediction, as well as improved vaccine coverage in that population.
    Also, I wonder if there have been any recent programs to track patterns in influenza strains using modern technology in genetics. Given the significance of this disease around the world, it could be a worthy cause.

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    1. Great proposal Jessica! Fortunately, there are recent programs out there that primarily focus on specific patterns of influenza strains around the world on a genetic level. One worth highlighting is The World Health Organization Global Influenza Surveillance Network, which has collected information on the migratory patterns and specific location of the different strains, developed an "antigenic map" to visually depict the dynamics between all the virus strains.

      http://www.sciencemag.org/cgi/content/full/320/5874/340; https://www.sciencedaily.com/releases/2008/05/080519165939.htm

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