The document provides information about influenza viruses, specifically focusing on Influenza A, B, and C. It discusses the differences between these types of influenza viruses in terms of their hosts, RNA segments, ability to cause antigenic drift or shift, and ability to cause pandemics or epidemics. It also summarizes past influenza pandemics and provides details about the 2009 H1N1 pandemic. Furthermore, it outlines recommendations for preventing and responding to influenza pandemics according to the WHO pandemic phases.

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2. Prepared by Dr.shereen Bahgat Dr.Randa Said Dr.Yasmin Elhussieny Prof.Dr.Adel Fouda

4. Influenza viruses family Orthomyxoviridae myxo=mucus) 3 distinct types According to differences in internal proteins (NP &M): Influenza A Influenza B Influenza C (Common Cold)

5. Influenza A Multiple Hosts Human, swine, avian, equine in worm blooded animals (birds & mammals including pigs and horses) 8 viral RNA segments Antigenic Drift Antigenic Shift Pandemics Epidemics/Seasonal Flu Influenza B Humans only 8 viral RNA segments Antigenic Drift ONLY No Antigenic SHIFT Not causing pandemics Epidemics/Seasonal Flu Influenza C Humans only 7 viral RNA segments No Antigenic Drift No Antigenic SHIFT cause mild illness don't cause epidemic or pandemic (sporadic)

6. Antigenic Drift Small variation Occurs frequently (1-2 yr) Epidemics/Seasonal Flu Antigenic Shift Large variation No immunity in population Pandemics

8. Influenza A Influenza A Subtypes based on surface glycoprotein : Hemaglutanin (HA) – viral attachment/entry Neuraminidases (NA) – enable virus to be released from the host cell Influenza A subdivided into types based on HA and NA there are 16 HA and 9 NA

9. Immunity to infection based on antibodies to viral surface antigens HA and NA An individual virus strain is identified by the subtypes of H and N proteins on its surface. It is named by the letters H and N, each followed by the number of the subtype.

10. pandemic Multiple areas affected at the same time. More difficult to borrow resources. Could go on for months in a community, with 2-3 different waves over 18-24 mo. Healthcare system will be overwhelmed. Preventive and therapeutic agents delayed and in short supply. Vaccine may not be available for at least 6 months

11. Influenza pandemics Spanish flu 1918 Asian flu 1957 Hong Kong flu 1968 virus A(H1N1) 40-50 million death 50% victim young healthy people die in a few days virus A(H2N2) China, Feb 1957 spread to USA in 4 months 1 million death virus A(H3N2) Honking, early 1968 spread quickly to USA still circulate today

12. 2009-H1N1 Pandemic: Situation Update Mexico, mid-April 2009 Novel virus Little to no immunity in population Widespread disease reported WHO declared pandemic, June 2009

13. WHO Pandemic Influenza Preparedness and Response Guidance 2009 Phase 1 No animal influenza virus circulating among animals has been reported to cause infection in humans Phase 2 An animal influenza virus circulating in domesticated or wild animals is known to have caused infection in humans and is therefore considered specific potential pandemic threat Phase 3 An animal or human-animal reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community–level outbreaks Phase 4 Human-to-human transmission of an animal or human-animal influenza reassortant virus able to sustain community-level outbreaks has been verified Phase 5 The same identified virus has caused sustained community-level outbreaks in two or more countries in one WHO region Phase 6 In addition to criteria defined in phase 5, the same virus has caused sustained community level outbreaks in at least one other country in another WHO region

14. Flu pandemic phase

15. Swine flu, the facts

16. H1N1

19. H1N1 (2009) Influenza

20. Genetics of Swine flu H1N1 Code Protein Source Origin HA Hemagglutinin swine (H1) North America NA Neuraminidase swine (N1) Europe PA Polymerase Acid avian North America PB1 Polymerase Basic Subunit 1 human 1993 H3N2 strain PB2 Polymerase Basic Subunit 2 avian North America NP Nucleoprotein swine North America M Matrix protein M1, M2 swine Eurasia NS Non-structural proteins NS1, NEP swine North America

22. How is the H1N1 (swine) flu different from seasonal flu? Unlike with the seasonal flu, young people are at higher risk of H1N1 infection than people 65 and older. However, infected people 65 or older are still at increased risk of H1N1 influenza-related complications. The worldwide spread of the H1N1 virus this spring was both rapid and unusual as it affected some countries outside of the time frame of a normal flu season. While most people who have become ill with the H1N1 virus have recovered without needing medical treatment, hospitalizations and deaths have occurred.

23. Comparison human avian swine Etiology H2N3 H5N1 H1N1 Epidemiology Seasonal Pandemic threat Pandemic phase 5 Transmission Human to human Animal to human Human to human Morbidity High Low High Clinical Mild to severe, usually mild Similar to human, Many severe fatal Similar to human, usually mild Mortality Low High Low Treatment Oseltamivir Oseltamivir Oseltamivir

24. Distribution of virus as regard time, place and person Time: The 1 st wave was in April 2009 (warm month) The 2 nd wave is expected in January and February 2010 (cold month) Place: Optimal temperature is 18˚c where it can live for 1 week. The virus can live 12 hours or longer in room temperature on surfaces like cafeteria tables, doorknobs, and desks. At 44˚c the virus died. At -3˚c the virus is inactivated

25. Person (High-Risk Groups): These groups of people are at risk of complications of influenza and are high priority for vaccination: 1. Pregnant women or women up to 4 weeks post-partum. 2. People with the following conditions: Chronic pulmonary conditions (asthma, COPD, cystic fibrosis) Chronic cardiac (heart) conditions. Except hypertension. Renal, hepatic disease. (kidney/liver) Sickle cell disease. Neurologic or neuromuscular disorders (compromise ability to clear airway secretions)

26. Diabetes mellitus and other metabolic disorders Morbid Obesity Immunosuppressant (caused by medications or HIV). 3. Persons younger than 19 yrs who are receiving long-term aspirin therapy. 4. Children younger than 5 yrs old. The risk for severe complications from seasonal influenza is highest among children younger than 2 years old. 5. Persons aged 65 yrs. and over with co morbid conditions.

27. Swine Influenza A(H1N1) Transmission to Humans Through contact with infected pigs or environments contaminated with swine flu viruses Through contact with a person with swine flu Human-to-human spread of swine flu has been documented also and is thought to occur in the same way as seasonal flu, through coughing or sneezing of infected people

29. Transmission This virus is transmitted in ways similar to other influenza viruses Human influenza viruses are spread from person to person primarily through large-particle droplet transmission (e.g., coughs or sneezes) Droplets requires close contact (<1 meter) between source and recipient persons Contaminated surfaces is another possible source of transmission All respiratory secretions and bodily fluids (diarrheal stool) of swine flu cases should be considered potentially infectious CDC 2009, Guidance on identifying & caring

30. Infectious period The duration of shedding with swine flu A (H1N1) virus is unknown considered potentially contagious for up to 7 days following illness onset children, especially younger children, might be contagious for longer periods Increases in cases of chronic tonsillitis or chronic URT infection. CDC 2009, Guidance on identifying & caring

31. Incubation period The estimated incubation period is unknown and could range from 1-7 days, and more likely 2-3 days CDC 2009, Guidance on identifying & caring

33. Symptoms in virologically confirmed cases Cough (98%); Subjective fever (96%); Fatigue (89%); Headache (82%); Sore throat (82%); Abdominal pain (50%); Diarrhea (48%); Dyspnea (48%); and Joint pain (46%).

34. CDC case definition Acute febrile respiratory illness temperature 38C & recent onset of at least 1 of the following: rhinorrhea or nasal congestion, sore throat, or cough. A suspected case : A person with acute febrile respiratory illness with onset Within 7 days of close contact with a person who is a confirmed case, OR Within 7 days of travel to community where there are one or more confirmed cases, OR Resides in a community where there are one or more confirmed cases .

35. CDC case definition A 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 A confirmed case : A person with an acute febrile respiratory illness with laboratory confirmed : Real-time RT-PCR Viral culture

36. Acute pneumonia temperature ≥38˚ or <35.5 and chills. WBCs > 11,000 or < 3000 Plus one of the following: Abnormal breathing sounds on the chest Chest pain, Cough and bloody sputum Tachypnia: infant 2 ms > 60 2-12 ms> 50 12ms-5yrs>40 >5yrs>20

37. Complications of H1N1 Influenza Exacerbation of underlying chronic disease; Complications related to the upper airways, including sinusitis or otitis; Pulmonary complications, including bronchitis, asthma (sometimes with status asthmaticus), and acute exacerbations of chronic bronchitis

38. Miscellaneous conditions, including cardiac (myocarditis and pericarditis), myositis, rhabdomyolysis, central nervous system complications (encephalopathy, encephalitis, seizures), toxic shock syndrome, and secondary bacterial pneumonia.

39. Diagnostic testing Rapid enzyme immunoassay Type A: seasonal or new H1N1 Sensitivity for new H1N1 ~75% PCR diagnostic kit available↗ High-risk for complications Severe or hospitalized cases. viral culture Real time ↘ conventional N.B. Real time is better than conventional The result takes 8 hrs to be released.

40. CDC Swab kit available Method: Horizontal, away from nasal septum

43. Three C’s Clean Cover Contain

44. Cover your mouth and nose Cover your mouth and nose with a tissue when coughing or sneezing. It may prevent those around you from getting sick

45. How to wear the mask? ×

46. Types of Protective Masks Surgical masks Easily available and commonly used for routine surgical and examination procedures High-filtration respiratory mask Special microstructure filter disc to flush out particles bigger than 0.3 micron. These masks are further classified: • oil proof • oil resistant • not resistant to oil The more a mask is resistant to oil, the better it is The masks have numbers beside them that indicate their filtration efficiency. For example, a N95 mask has 95% efficiency in filtering out particles greater than 0.3 micron under normal rate of respiration. The next generation of masks use Nano-technology which are capable of blocking particles as small as 0.027 micron.

47. Clean Hands saves you Clean your hands often. Clean your hands every time you cough or sneeze. Hand washing stops germs. Alcohol-based gels and wipes also work well.

48. Clean your hands. Washing your hands often will help protect you from germs. Hand washing proved to be best procedure in prevention of Majority of Communicable diseases.

49. Avoid touching your eyes, nose or mouth. Germs are often spread when a person touches something that is contaminated with germs and then touches his or her eyes, nose, or mouth.

50. Avoid close contact Avoid close contact with people who are sick. When you are sick, keep your distance from others to protect them from getting sick too. Aerosols spread the virus in any environment

51. Stay home when you are sick . If possible, stay home from work, school, and errands when you are sick. You will help prevent others from catching your illness

52. Practice other good health habits. Get plenty of sleep, be physically active, manage your stress, drink plenty of fluids, and eat nutritious. Unnecessary Migration of people from epidemic and endemic areas to be reduced

56. Healthy Habits reduces the Attacks

57. Vaccination A flu vaccine is the single best way to protect against influenza illness. This season, there is a seasonal flu vaccine to protect against seasonal flu viruses and a 2009 H1N1 vaccine to protect against the 2009 H1N1 influenza virus (sometimes called “swine flu”).

59. A 2009 H1N1 &quot;flu shot&quot; An inactivated vaccine (containing killed virus) that is given with a needle, usually in the arm. The indications for who can get the 2009 H1N1 flu shot are the same as for seasonal flu shots. The flu shot is approved for use in people 6 months of age and older, including healthy people, people with chronic medical conditions and pregnant women. The same manufacturers who produce seasonal flu shots are producing 2009 H1N1 flu shots for use in the United States this season. The 2009 H1N1 flu shot is being made in the same way that

60. The 2009 H1N1 nasal spray flu A vaccine made with live, weakened viruses that do not cause the flu (sometimes called LAIV for &quot;live attenuated influenza vaccine&quot;). The indications for who can get the 2009 H1N1 nasal spray vaccine are the same as for seasonal nasal spray vaccine. LAIV is approved for use in healthy* people 2 years to 49 years of age who are not pregnant.

61. Initial Target Groups Are: Pregnant women People who live with or provide care for infants younger than 6 months (e.g., parents, siblings, and day care providers), Health care and emergency medical services personnel People 6 months through 24 years of age (especially those with higher risk for influenza-related complications like children younger than 5 years and those who have high risk medical conditions), and, People 25 years through 64 years of age who have certain medical conditions that put them at higher risk for influenza-related complications

62. When to Get Vaccinated Vaccination against 2009 H1N1 should begin as soon as vaccine is available and continue throughout the influenza season, into December, January, and beyond. This is because the timing and duration of flu activity can vary. Flu seasons can last as late as April or May

63. Vaccine dosing Persons ≥10 years: single dose; Children > 35 months to 10 years: 2 doses separated by 21-28 days; and Children 6-35 months: 2 vaccinations that contain half the standard dose used for older children and adults; the interval between vaccinations should be 21-28 days.

64. To whom vaccine is contraindicated? Less than 6 mons Sensitivity to egg Sever allergic conditions Allergy to seasonal vaccine Acute sever conditions

65. Vaccine Effectiveness The ability of a flu vaccine to protect a person depends on the age and health status of the person getting the vaccine, and the similarity or &quot;match&quot; between the viruses or virus in the vaccine and those in circulation. CDC analyzes circulating influenza viruses on an ongoing basis to determine how closely matched they are to vaccine viruses and publishes the information weekly in FluView .

66. Vaccine Side Effects (What to Expect) Vaccine Side Effects (What to Expect) The same side effects typically associated with the seasonal flu shot and the seasonal nasal spray vaccine are expected with the 2009 H1N1 flu shot and 2009 H1N1 nasal spray vaccine.

67. The flu shot Some minor side effects that could occur are: Soreness, redness, or swelling where the shot was given Fever (low grade) Aches If these problems occur, they begin soon after the shot, are usually mild, and usually last 1 to 2 days. Almost all people who receive influenza vaccine have no serious problems from it. However, on rare occasions, flu vaccination can cause serious problems, such as severe allergic reactions.

68. The nasal spray The viruses in the nasal-spray vaccine are weakened and do not cause severe symptoms often associated with influenza illness. (In clinical studies, transmission of vaccine viruses to close contacts has occurred only rarely.)

69. Children, side effects from LAIV can include Runny nose Wheezing Headache Vomiting Muscle aches Fever

70. Adults, side effects from LAIV can include Runny nose Headache Sore throat Cough

71. Treatment H1N1 flu is sensitive to the antiviral drugs Tami flu and Relenza . Antiviral aren’t usually necessary for mild illness (except perhaps for those who are at high risk for complications) Rest and fluids work best Should be started early for maximum effectiveness State/federal stockpiles have been sent to designated providers

72. Effectiveness In the 1 st 48 hrs gives 98% effect. Decreased with time.

73. WARNING! Do not treat children with ASPIRIN Aspirin treatment in children with the flu or other viral infections has a known association with Reyes Syndrome – a potentially fatal complication

75. Oseltamivir Administration Route of Administration Administer orally For Treatment Administer within 48 hours of symptom onset For Prophylaxis Give to close contacts within 48 hours of exposure

76. Pharmacology Absorption : Well-absorbed orally with over 80'% bioavailability of active form oseltamivir phosphate Plasma half-life: of active form averages 8-10 hours  twice daily dosing for treatment and once daily for prophylaxis Metabolism : hepatic esterases Elimination : renal elimination &exceed G F R indicate tubular secretion dose reduction for renal failure (CrCl < 30 ml/min) No important adverse drug interactions Probenicid delays excretion

77. Oral Formulations Capsules 75 mg each 10 capsules per box Manufacturer: Roche Brand name—Tamiflu® Store at room temperature (15 - 30 0 C) Liquid Suspension White powder mixed with 23 mL of drinking water Fruit flavored Refrigeration required Use within 10 days Oral dispenser included

78. Treatment Regimen Adults : 75 mg two times a day for 5 days(13 year & more Not approved for children less than 1 year of age Children > 1 year old: (children &who cannot swallow tablets) <15 kg: 30 mg twice daily 15 - <23 kg: 45 mg twice daily for 5 days 23 - <40 kg: 60 mg twice daily > 40 kg: 75 mg twice daily In sever cases double dose and period.

79. Chemoprophylaxis Doses Duration of prophylaxis depends on epidemiologic setting. Post-exposure use is typically for 7 to 10 days. Patient Age Prophylactic Dose > 13 years 1 capsule (75 mg) once a day 1 to 12 years < 15 kg: 30 mg once a day 15-<23 kg: 45 mg once a day 23-<40 kg: 60 mg once a day > 40 kg: 75 mg once a day

80. NA inhibitors Mechanism of Action

81. Side Effects Headache (20%)* Nausea (10%) Vomiting (9%) Fatigue (8%)* Diarrhea (7%) Cough (6%)* Bronchitis, abdominal pain, dizziness (2%) Insomnia, vertigo (1%)\ Rarely: Allergic reactions Skin rash (sometimes severe) Facial swelling Dizziness Hepatitis

82. Contraindications & Precautions Pregnant or breastfeeding mothers No recognized birth defects in pre-clinical testing in animals No human clinical studies demonstrating safety or efficacy Use if benefit outweighs risk Liver disease Safety and efficacy not yet evaluated Kidney disease Decrease dose based on creatinine clearance

83. Chemoprophylaxis Not routinely encouraged Increases risk of antiviral drug resistance Reserved for high risk persons Versus education, close monitoring of symptoms PLUS early treatment

84. Now a days resistant cases to Tamiflu had appeared but still sensitive t o Relenza

85. Situation in Egypt Case fatality is reported to be 1.8% (compared with 0.3% in Europe and 2.4% for the 1918-19 influenza pandemic). Number of cases:

86. National policy Leadership and governing Virus monitoring Proactive measures VS containment Passive disease surveillance Training and communication School suspension

87. Proactive measures VS containment

91. School suspension 2-4 weeks:(2 of 3 conditions) ↑ no. of cases by 2, 4, 8 every week LRTI in 5-10% Case fatality 2% 4-12 weeks: ↑ no. of cases by 2, 4, 8 in one week LRTI more than 10% Case fatality >2%

93. case swab tamiflu hospital home note <5yrs +mild symp. √ √ detoriarated->hospital <5yrs +sever symp. √ √ √ >65yrs +mild symp. √ √ detoriarated->hospital <65yrs +sever symp √ √ √ Pregnant +mild symp √ √ detoriarated->hospital Pregnant +sever symp √ √ √ Chronic disease+mild symp √ √ detoriarated->hospital Chronic disease+ sever symp √ √

94. case swab tamiflu hospital home note 5-65+seve symp √ √ √ mild+ good isolated room √ detoriarated->hospital mild+ bad isolated room √ √ √ pneumonia √ √ √ Acute sever chest infection √ √ √ Suspect avian √ √ √ Separate isolated room

95. ++