به نام خدا

1. به نام خدا

2. influenza

3. دكتر محمد امامي فوق تخصص ريه و مراقبتهاي ويژه عضو هيات علمي دانشگاه

4. Influenza

5. Definition • Etiologic Agent • Epidemiology • Pathogenesis and Immunity • Clinical Manifestations • Complications • Laboratory Findings and Diagnosis • Differential Diagnosis • Treatment • Prophylaxis

6. Definition • Influenza is an acute respiratory illness caused by infection with influenza viruses

7. Etiologic Agent • Orthomyxoviridae family • single-stranded RNA genome • classified into three distinct types: influenza A • influenza B • influenza C virus • based on major antigenic differences • host cell–derived envelope

8. H N Influenza Type A Subtypes

9. Virus Structure

10. The standard nomenclature for influenza viruses includes : • the influenza type • place of initial isolation • strain designation • year of isolation

11. For example, an influenza A virus isolated from a patient in Puerto Rico in 1934 is given the strain designation A/PuertoRico/8/34, sometimes referred to as “PR8” virus.

12. Influenza A viruses are further subdivided (subtyped) on the basis of the surface hemagglutinin (H) and neuraminidase (N) antigens • Influenza A has 16 distinct H subtypes and 9 distinct N subtypes • only H1, H2, H3, N1, and N2 have been associated with epidemics of disease in humans

13. Influenza A and B viruses are major human pathogens • Type A and type B viruses are morphologically similar • The hemagglutinin is the site by which the virus binds to sialic acid cell receptors, whereas the neuraminidase degrades the receptor and plays a role in the release of the virus from infected cells after replication has taken place

14. Immune responses to the H antigen are the major determinants of protection against infection with influenza virus, while those to the N antigen limit viral spread and contribute to reduction of the infection.

15. Infection with influenza virus results in long-lived resistance to reinfection with the homologous virus. • Infection induces both systemic and local antibody, as well as cytotoxic T-cell responses, each of which plays a role in recovery from infection and resistance to reinfection.

16. Epidemiology • Influenza outbreaks are recorded virtually every year, although their extent and severity vary widely • Localized outbreaks take place at variable intervals, usually every 1–3 years. Global pandemics have occurred at variable intervals, but much less frequently than interpandemic outbreaks

17. Influenza A outbreaks typically begin abruptly, peak over a two to three week period, and last for two to three months • . In most outbreaks, the earliest indication of influenza activity is an increase in febrile respiratory illnesses in children, followed by increases in influenza-like illnesses in adults. Increases in absenteeism from work and school are usually later manifestations of outbreaks

18. Most outbreaks have attack rates of 10 to 20 percent in the general population, but rates can exceed 50 percent in pandemics • Extraordinarily high attack rates have been reported in institutionalized and semiclosed populations.

19. History: Known Flu Pandemics Information taken from en.wikipedia.org/wiki/influenza

20. 1918 Flu Pandemic • American Red Cross nurses tend to flu patients in temporary wards set up inside the Oakland municipal Auditorium. http://en.wikipedia.org/wiki/Image:1918_flu_in_Oakland.jpg

21. Influenza virus infection is acquired by transfer of virus-containing respiratory secretions. Both small-particle aerosols and droplets probably play a role in this transmission, but for infection control purposes influenza is generally considered to be transmitted by droplets

22. In temperate climates in either hemisphere, epidemics occur almost exclusively in the winter months (generally October to April in the Northern hemisphere and May to September in the Southern hemisphere), while influenza may be seen year round in the tropics.

23. Influenza epidemics are regularly associated with excess morbidity and mortality, usually expressed in the form of excess rates of pneumonia and influenza-associated hospitalizations and deaths

24. Attack rates are generally highest in the young, whereas mortality is generally highest in the elderly • Excess morbidity and mortality are particularly high in those with medical conditions including pulmonary conditions such as asthma or COPD. Rates of influenza-related hospitalizations are particularly high in healthy children under 2 years of age.

25. A high frequency of antigenic variation is a unique feature of influenza virus that helps to explain why this virus continues to cause epidemic disease

26. Antigenic drift • relatively minor antigenic changes that result from amino acid changes in one or more of the five identified major antigenic sites on the HA molecule.

27. Antigenic shift • complete replacement of the HA or NA with a novel HA or NA. • These viruses are “new” viruses to which the population has no immunity • antigenic shifts, are seen only with influenza A viruses and may be associated with pandemics.

28. Influenza B virus causes outbreaks that are generally less extensive and are associated with less severe disease than those caused by influenza A virus. The hemagglutinin and neuraminidase of influenza B virus undergo less frequent and less extensive variation than those of influenza A viruses

29. Influenza B outbreaks are seen most frequently in schools and military camps, although outbreaks in institutions in which elderly individuals reside have also been noted on occasion. • The most serious complication of influenza B virus infection is Reye's syndrome.

30. In contrast to influenza A and B viruses, influenza C virus appears to be a relatively minor cause of disease in humans. It has been associated with common cold–like symptoms and occasionally with lower respiratory tract illness

32. Pathogenesis and Immunity • Infection with influenza virus in humans is generally limited to the respiratory tract. • After inoculation, the incubation period is thought to be from 18 to 72 hours, depending in part on the inoculum dose. • Virus shedding is maximal at the onset of illness and may continue for 5 to 7 days or longer in children.

33. diffuse inflammation of the larynx, trachea, and bronchi, and a range of histologic findings • Initially, viral infection involves the ciliatedcolumnar epithelial cells • Generally, the tissue response becomes more prominent as one moves distally in the airway. Recovery is associated with rapid regeneration of the epithelial cell layer, and pseudometaplasia.

34. Method of Infection and Replication: • The flu virus binds onto sugars on the surfaces of epithelial cells such as nose, throat, and lungs of mammals and intestines of birds. http://en.wikipedia.org/wiki/Image:Virus_Replication_large.svg

35. The host response to influenza infections involves a complex interplay of humoral antibody, local antibody, cell-mediated immunity, interferon, and other host defenses. • Serum antibody responses, which can be detected by the second week after primary infection • Antibodies to the hemagglutinin appear to be the most important mediators of immunity • Virus shedding generally stops within 2–5 days after symptoms first appear

36. Clinical Manifestations • incubation period of 1 to 2 days • an abrupt onset of symptoms • Systemic symptoms include feverishness, chilliness or frank shaking chills, headaches, myalgia, malaise, and anorexia. • dry cough, severe pharyngeal pain, and nasal obstruction and discharge • Elderly individuals may simply present with fever, lassitude, and confusion without the characteristic respiratory complaints, which may not occur at all.

37. the spectrum of clinical presentations is wide, ranging from a mild, afebrile respiratory illness similar to the common cold (with either a gradual or an abrupt onset) to severe prostration with relatively few respiratory signs and symptoms

38. In most of the cases that come to a physician's attention, the patient has a fever, with temperatures of 38°–41°C (100.4°–105.8°F). • A rapid temperature rise within the first 24 h of illness is generally followed by gradual defervescence over 2–3 days, although, on occasion, fever may last as long as 1 week. • Patients report a feverish feeling and chilliness, but true rigors are rare. • Headache, either generalized or frontal, is often particularly troublesome • Myalgias may involve any part of the body but are most common in the legs and lumbosacral area. • Arthralgias may also develop.

39. Respiratory symptoms often become more prominent as systemic symptoms subside • Examination of the pharynx may yield surprisingly unremarkable results despite a severe sore throat • Mild cervical lymphadenopathy may be noted, especially in younger individuals

40. In uncomplicated influenza, the acute illness generally resolves over 2–5 days, and most patients have largely recovered in 1 week • cough may persist 1–2 weeks longer. • symptoms of weakness or lassitude (postinfluenza asthenia) may persist for several weeks

42. Persons at Higher Risk for Complications of Influenza • Children from birth to 4 years old • Pregnant women • Persons 65 years old • Children and adolescents (6 months to 18 years old) who are receiving long-term aspirin therapy and therefore may be at risk for developing Reye's syndrome after influenza • Adults and children who have chronic disorders of the pulmonary or cardiovascular system, including asthma • Adults and children who have chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunodeficiency (including immunodeficiency caused by medications or by HIV) • Adults and children who have any condition that can compromise respiratory function or compromise the handling of respiratory secretions or can increase the risk of aspiration • Residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions

43. Complications • Pulmonary Complications • Extrapulmonary Complications

44. Pulmonary Complications • Pneumonia • The most significant complication of influenza is pneumonia • 1-primary" influenza viral pneumonia • 2- secondary bacterial pneumonia • 3- mixed viral and bacterial pneumonia

45. Primary Influenza Viral Pneumonia • least common but most severe of the pneumonic complications • Primary influenza viral pneumonia has a predilection for individuals with cardiac disease, particularly those with mitral stenosis, but has also been reported in otherwise-healthy young adults as well as in older individuals with chronic pulmonary disorders. In some pandemics of influenza pregnancy increased the risk of primary influenza pneumonia

46. Secondary Bacterial Pneumonia • The most common bacterial pathogens in this setting are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilusinfluenzae • Secondary bacterial pneumonia occurs most frequently in high-risk individuals with chronic pulmonary and cardiac disease and in elderly individuals.

47. Mixed Viral and Bacterial Pneumonia • Many patients present with mixed viral and bacterial pneumonia • Mixed viral and bacterial pneumonia occurs primarily in patients with chronic cardiovascular and pulmonary diseases

48. Other Pulmonary Complications • worsening of chronic obstructive pulmonary disease • exacerbation of chronic bronchitis and asthma. • In children, influenza infection may present as croup • Sinusitis as well as otitis media (the latter occurring particularly often in children) may also be associated with influenza.

49. Extrapulmonary Complications • Reye's syndrome • Myositis • rhabdomyolysis • myoglobinuria • Myocarditis • pericarditis • Encephalitis • transverse myelitis • Guillain-Barré syndrome