INFLUENZA INFECTION By M Osama Hussein. MD

Credit: L. Stammard, 1995Influenza Virus

*The internal antigens (M1 and NP proteins) are the type-specific proteins (type-specific antigens) used to determine if a particular virus is A, B or C. The M1 proteins of all members of each type show cross reactivity. The NP proteins of all members of each type also show cross reactivity.The external antigens (HA and NA) show more variation and are the subtype and strain-specific antigens. These are used to determine the particular strain of influenza A responsible for an outbreakFlu strains are named after their types of hemagglutinin and neuraminidase surface proteins, so they will be called, for example, H3N2 for type-3 hemagglutinin and type-2 neuraminidase. If two different strains of influenza infect the same cell simultaneously, their protein capsids and lipid envelopes are removed, exposing their RNA, which is then transcribed to mRNA. The host cell then forms new viruses that combine antigens; for example, H3N2 and H5N1 can form H5N2 this way. Because the human immune system has difficulty recognizing the new influenza strain, it may be highly dangerous.

Sheet1

Natural hosts of influenza viruses

Haemagglutinin subtypeNeuraminidase subtype

H1N1

H2N2

H3N3

H4N4

H5N5

H6N6

H7N7

H8N8

H9N9

H10

H11

H12

H13

H14

H15

H16

Sheet2

Sheet3

*Influenza A viruses are found in many different animals, including ducks, chickens, pigs, whales, horses, and seals. There are 16 different haemaglutinin subtypes and 9 different neuraminidase subtypes, all of which have been found among influenza A viruses in wild birds. Wild birds are the primary natural reservoir for all subtypes of influenza A viruses and are thought to be the source of influenza A viruses in all other animals. Most influenza viruses cause asymptomatic or mild infection in birds; however, the range of symptoms in birds varies greatly depending on the strain of virus. Infection with certain avian influenza A viruses (for example, some strains of H5 and H7 viruses) can cause widespread disease and death among some species of wild and especially domestic birds such as chickens and turkeys.Pigs can be infected with both human and avian influenza viruses in addition to swine influenza viruses. Infected pigs get symptoms similar to humans, such as cough, fever, and runny nose. Because pigs are susceptible to avian, human and swine influenza viruses, they potentially may be infected with influenza viruses from different species (e.g., ducks and humans) at the same time. If this happens, it is possible for the genes of these viruses to mix and create a new virus.

Epidemic a located cluster of casesPandemic worldwide epidemicAntigenic drift

Changes in proteins by genetic point mutation & selection Ongoing and basis for change in vaccine each yearAntigenic shift

Changes in proteins through genetic reassortmentProduces different viruses not covered by annual vaccineDefinitions

*

Influenza The Normal Burden of DiseaseSeasonal Influenza

Globally: 250,000 to 500,000 deaths per yearIn the US (per year)~35,000 deaths>200,000 Hospitalizations$37.5 billion in economic cost (influenza & pneumonia)>$10 billion in lost productivityPandemic Influenza

An ever present threat

Reassortment in PigsSwine Influenza A(H1N1) Transmission Through Species

Reassortment, or Viral Subunit Reassortment, is the exchange of DNA between viruses inside a host cell. Two or more viruses of different strains (but usually the same species) infect a single cell and pool their genetic material creating numerous genetically diverse progeny viruses. It is a type of genetic recombination.Reassortment can lead to a viral shifts under some conditions.

Swine Influenza A(H1N1) Global ResponseSource: WHO

WHO Definition of Phases Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause community-level outbreaks. The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should urgently consult with WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion. Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short. Phase 6, the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.During the post-peak period, pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave. Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave. Pandemic waves can be separated by months and an immediate at-ease signal may be premature. In the post-pandemic period, influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required.

Source: WHO

Influenza SymptomsInfluenza (also known as the flu) is a contagious respiratory illness caused by flu viruses. It can cause mild to severe illness, and at times can lead to death. The flu is different from a cold. The flu usually comes on suddenly.

Influenza SymptomsFever* or feeling feverish/chillsCoughSore throatRunny or stuffy noseMuscle or body achesHeadachesFatigue (tiredness)Vomiting and diarrhea, children

Swine Influenza A(H1N1) Guidelines for General PopulationCovering nose and mouth with a tissue when coughing or sneezing

Dispose the tissue in the trash after use. Handwashing with soap and water

Especially after coughing or sneezing. Cleaning hands with alcohol-based hand cleaners Avoiding close contact with sick peopleAvoiding touching eyes, nose or mouth with unwashed handsIf sick with influenza, staying home from work or school and limit contact with others to keep from infecting them

Recommendations for Prevention and Control of Influenza in Children, 20162017COMMITTEE ON INFECTIOUS DISEASES

PediatricsSeptember 2016From the American Academy of PediatricsPolicy Statement

1. Annual universal influenza immunization is indicated with either a trivalent or quadrivalent (no preference) inactivated vaccine.

2. The 20162017 influenza A (H3N2) vaccine strain differs from that contained in the 20152016 seasonal vaccines. The 20162017 influenza B vaccine strain (Victoria lineage) included in the trivalent vaccine differs from that contained in the 20152016 seasonal trivalent vaccines (Yamagata lineage).

3. Quadrivalent live attenuated influenza vaccine (LAIV4) should not be used in any setting during the 20162017 influenza season in light of the evidence for poor effectiveness of LAIV4 in recent seasons, particularly against influenza A (H1N1)pdm09 viruses.

4. All children with egg allergy can receive influenza vaccine with no additional precautions from those of routine vaccinations.

5. All HCP should receive an annual influenza vaccine, a crucial step in preventing influenza and reducing health careassociated influenza infections. Because HCP may care for or live with people at high risk of influenza-related complications, it is especially important for them to get vaccinated annually.

6. Pediatricians should attempt to promptly identify children suspected of having influenza for rapid antiviral treatment, when indicated, to reduce morbidity and mortality.

Prevention and Control of Seasonal Influenza with VaccinesRecommendations of the Advisory Committee on Immunization Practices United States, 201617 Influenza SeasonAugust 26, 2016 / Grohskopf, et alRoutine annual influenza vaccination is recommended for all persons aged 6 months who do not have contraindications.

live attenuated influenza vaccine (LAIV4) should not be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate.

*The internal antigens (M1 and NP proteins) are the type-specific proteins (type-specific antigens) used to determine if a particular virus is A, B or C. The M1 proteins of all members of each type show cross reactivity. The NP proteins of all members of each type also show cross reactivity.The external antigens (HA and NA) show more variation and are the subtype and strain-specific antigens. These are used to determine the particular strain of influenza A responsible for an outbreakFlu strains are named after their types of hemagglutinin and neuraminidase surface proteins, so they will be called, for example, H3N2 for type-3 hemagglutinin and type-2 neuraminidase. If two different strains of influenza infect the same cell simultaneously, their protein capsids and lipid envelopes are removed, exposing their RNA, which is then transcribed to mRNA. The host cell then forms new viruses that combine antigens; for example, H3N2 and H5N1 can form H5N2 this way. Because the human immune system has difficulty recognizing the new influenza strain, it may be highly dangerous.

*Influenza A viruses are found in many different animals, including ducks, chickens, pigs, whales, horses, and seals. There are 16 different haemaglutinin subtypes and 9 different neuraminidase subtypes, all of which have been found among influenza A viruses in wild birds. Wild birds are the primary natural reservoir for all subtypes of influenza A viruses and are thought to be the source of influenza A viruses in all other animals. Most influenza viruses cause asymptomatic or mild infection in birds; however, the range of symptoms in birds varies greatly depending on the strain of virus. Infection with certain avian influenza A viruses (for example, some strains of H5 and H7 viruses) can cause widespread disease and death among some species of wild and especially domestic birds such as chickens and turkeys.Pigs can be infected with both human and avian influenza viruses in addition to swine influenza viruses. Infected pigs get symptoms similar to humans, such as cough, fever, and runny nose. Because pigs are susceptible to avian, human and swine influenza viruses, they potentially may be infected with influenza viruses from different species (e.g., ducks and humans) at the same time. If this happens, it is possible for the genes of these viruses to mix and create a new virus.*

Reassortment, or Viral Subunit Reassortment, is the exchange of DNA between viruses inside a host cell. Two or more viruses of different strains (but usually the same species) infect a single cell and pool their genetic material creating numerous genetically diverse progeny viruses. It is a type of genetic recombination.Reassortment can lead to a viral shifts under some conditions.WHO Definition of Phases Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause community-level outbreaks. The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should urgently consult with WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion. Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short. Phase 6, the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.During the post-peak period, pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave. Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave. Pandemic waves can be separated by months and an immediate at-ease signal may be premature. In the post-pandemic period, influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required.