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2. Influenza - Pathogenesis and Clinical manifestations.pptx
- 2. Bryn A Boslett, MD Division of Infectious Diseases University of California, San Francisco Influenza Pathogenesis and Clinical Manifestations 2
- 3. Learning Objectives • Describe the pathogenesis of influenza, specifically the transmission and lifecycle of the virus • Compare and contrast the clinical manifestations of influenza in relation to other viral pathogens and syndromes • List potential complications of influenza infection 3
- 4. Spread by large droplets, surfaces (hands!) and aerosol Pathogenesis
- 5. Incubation period: 1 – 4 days from time of exposure Pathogenesis
- 6. 1) Neuraminidase (NA) degrades protective mucus 2) Hemagglutinin (HA) binds cell surface receptors Pathogenesis
- 7. 3) Virus enters the cell and uncoats 4) Genome segments mRNAs within the nucleus Pathogenesis
- 8. 5) mRNA proteins (cytoplasm) or mRNA progeny (nucleus) Pathogenesis
- 9. 6) Viral particles assembled in cytoplasm 7) Virions released from cells by budding from cell membrane (with aide of NA) 8) Viral replication kills host cells Pathogenesis
- 10. 10 Anatomical Location of Viral Syndromes Lower Tract Trachea Bronchi Bronchioles Lung Bronchiolitis RSV Metapneumovirus Adenovirus Bronchitis Laryngotracheo-bronchitis Croup Parainfluenza Upper Tract Nasal Cavity Nasopharynx Oropharynx Larynx Pharyngitis Sore Throat Laryngitis Adenovirus, Parainfluenza Rhinitis Common Cold Rhinovirus, Coronavirus Parainfluenza, Adenovirus, Metapneumovirus RSV, Coronavirus Pneumonia All viruses
- 11. 11 Anatomical Location of Viral Syndromes Trachea Bronchi Bronchioles Lung Bronchiolitis RSV, Influenza, Metapneumovirus Adenovirus Bronchitis Laryngotracheo-bronchitis Croup Parainfluenza, Influenza Nasal Cavity Nasopharynx Oropharynx Larynx Pharyngitis Sore Throat Laryngitis Adenovirus, Parainfluenza Influenza Rhinitis Common Cold Rhinovirus, Coronavirus Influenza Parainfluenza, Influenza, Adenovirus, Metapneumovirus RSV, Coronavirus Pneumonia All, especially Influenza Upper Tract Lower Tract
- 12. Influenza clinical manifestations 12 • Incubation period after exposure: 1 – 4 days • Abrupt onset of fever, myalgias, headache, pharyngitis, rhinorrhea, cough and fatigue • 5 – 7 days of acute illness, full recovery may be prolonged • Most adults infectious for 3 – 5 days after symptom onset • Children may be infectious for 10 days or more • Immunocompromised may shed virus for several weeks
- 13. Complications - Pneumonia 13 • Primary influenza pneumonia respiratory failure in 10-20%! • Secondary bacterial pneumonia • Influenza “primes” lung tissues for bacterial infection • Patient may initially improve, then worsen • S. pneumoniae, S. aureus, H. influenza, nosocomial gram (-) rods
- 14. Complications - Reye’s syndrome 14 • Rare, life-threatening syndrome in children following some viral infections (influenza and varicella most commonly) • Fever, rash, encephalopathy, liver failure • Pathogenesis unclear, aspirin has been implicated
- 15. Credits: Pathogenesis and Clinical Manifestations 15 Slide 7: http://commons.wikimedia.org/wiki/File:Mexican_Catholics_at_the_Metropolitan_Cathedral_S wine_Flu.jpg http://commons.wikimedia.org/wiki/File:H1N1_USA_Map_by_confirmed_cases.svg Slide 8-9: http://commons.wikimedia.org/wiki/File:Sneeze.JPG Slide 16: http://en.wikipedia.org/wiki/Acute_respiratory_distress_syndrome#mediaviewer/File:AARDS_ X-ray_cropped.jpg Slide 21: http://commons.wikimedia.org/wiki/File:Regular_strength_enteric_coated_aspirin_tablets.jpg
Editor's Notes
- Title Slide Primary Header: Arial, Bold, 32pt. Sub Head: Arial, 24pt. Faculty Name: Arial, Bold, 24pt. Faculty Titles: Arial, 24pt Use Unit Primary Image if available Image: Drop Shadow Rectangle (35%, 100%, 23pt, 45 degree, 11pt)
- Learning Objectives– Text only Logo: 1” high by 1.02” wide. Horizontal .2, Vertical .2 Primary Header: Arial, Bold, 32pt. Bulleted List: Arial, 24pt. Single Spacing Limit text boxes to 5.75 inches width as maximum Image: Drop Shadow Rectangle (35%, 100%, 23pt, 45 degree, 11pt) (target 2 to 3 bullets maximum per slide)
- Influenza viruses are spread from person to person primarily through large-particle respiratory droplet transmission (in other words, when an infected person coughs or sneezes near a susceptible person, virus can exit the infected person and enter a new host). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60. MMWR July 13, 2007 / 56(RR06);1-54 Sneeze
- Transmission generally requires close contact between source and recipient persons, because droplets do not remain suspended in the air and generally travel only a short distance. Contact with contaminated surfaces is another possible source of transmission, as the virus can live on non-porous surfaces for up to 48 hours, and on clothing for up to 12 hours. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008 Aug 8;57(RR-7):1-60. MMWR July 13, 2007 / 56(RR06);1-54 Sneeze http://en.wikipedia.org/wiki/Sneeze
- Let’s review the pathogenesis of influenza virus infection. Once the virus is inhaled, NA helps to degrade the protective mucus layer, allowing the virus to invade host tissues by gaining access to underlying respiratory epithelium. This may be even easier in winter months, when cold air tends to dry out the mucous membranes. Upon making contact with the cell surface, HA binds neuraminic acid receptors and the virus enters the cell in vesicles.
- Once in the cell, viral uncoating occurs within cell endosomes. The virion genome moves to the nucleus, where replication takes place. Viral RNA polymerase transcribes the eight genome segments into eight mRNAs. Sneeze http://en.wikipedia.org/wiki/Sneeze
- Most of these mRNAs will enter the cytoplasm, where they will be translated into viral proteins. However, some mRNAs will remain in the nucleus, where they will serve as templates for the synthesis of negative-strand RNA genomes for progeny viruses. Sneeze http://en.wikipedia.org/wiki/Sneeze
- Progeny RNA genomes are transported to the cytoplasm, where newly synthesized proteins act to assemble virions. Progeny virions are released from the cell by budding off the outer cell membrane, at the site where the HA and NA are located. Recall that NA acts to release the virus by cleaving neuraminic acid on the cell surface at the site of the budding progeny. Thereafter, new viruses are free to infect neighboring epithelial cells. The virus will ultimately kill the host as it replicates, often leading to widespread necrosis of the superficial layers of respiratory epithelium.
- This graphic will be familiar to you if you’ve viewed our respiratory virus modules. Influenza infection is largely limited to the respiratory tract, and can produced a myriad of symptoms, including rhinitis, pharyngitis,, bronchitis and pneumonia.
- Although viremia (meaning, detectable virus in the blood) rarely occurs, the bodily aches and pains associated with influenza infection are what sets it apart from the other viral respiratory illnesses. These systemic symptoms are the result of circulating cytokines.
- The typical incubation period for influenza is between 1 and 4 days from the time of exposure (on average , about 2 days). The onset of influenza is typically sudden and abrupt. Patients can often remember the exact time at which they began to feel sick. Symptoms typically include fever, muscle pains called myalgias, headache, sore throat, stuffy nose called rhinorrhea, and cough. Patients may also feel very tired or fatigued. The acute illness typically lasts between 5 and 7 days, at which point the patient typically starts to improve, although fatigue and cough may last for several weeks afterwards. Adults shed influenza virus from approx. one day before symptoms begin through 5-10 days after illness onset. However, the amount of virus shed, and presumably infectivity, decreases rapidly by 3-5 days after onset in an experimental human infection models. Young children also might shed virus several days before illness onset, and children can be infectious for >10 days after onset of symptoms. Severely immunocompromised persons can shed virus for weeks or months. Content Slide – Text only Logo: 1” high by 1.02” wide. Horizontal .2, Vertical .2 Primary Header: Arial, Bold, 32pt. Bulleted List: Arial, 24pt. Single Spacing Limit text boxes to 9 inches width as maximum *Avoid orphans if possible. Break lines to prevent single words on a second line of a sentence. (target 4 to 6 bullets maximum per slide)
- As mentioned previously, influenza virus infection is associated with significant morbidity and mortality, particularly related to severe respiratory complications such as pneumonia. Primary influenza pneumonia, meaning pneumonia caused by direct infection of the lung parenchyma by the influenza virus, has a mortality rate of between 10 and 20%. Onset is often abrupt and dramatic, often progressing within 24 h to severe disease with respiratory failure, shock and death. Non-fatal cases typically recover within 1-2 weeks after pneumonia onset, but residual lung damage frequently occurs. Even more common than primary influenza pneumonia, secondary bacterial pneumonias or mixed viral + bacterial infections are a major complication of influenza. There is strong and consistent evidence of synergetic interaction between influenza and bacterial respiratory pathogens. Potential mechanisms for synergy include: virus damage and destruction of respiratory epithelium, which may increase bacterial adhesion; influenza virus neuraminidase activity, which disrupts mucus barriers and might also enhance bacterial adherence; and inflammatory responses to viral infection that may upregulate expression of molecules that are utilized as receptors by bacteria. With secondary bacterial pneumonia, patients’ influenza symptoms typically improve as expected, but then patients deteriorate with symptoms or signs suggestive of bacterial pneumonia, including chills, rigors, increased productive cough, pleuritic chest pain, and dyspnea. Mortality rate is approximately 7%. The most common bacterial etiologies are strep pneumonia and staph aureus, including MRSA, H. infleunzae are the most common pathogens, as well as gram negative organisms and other nosocomial (meaning healthcare associated) pathogens. Content Slide – Text only Logo: 1” high by 1.02” wide. Horizontal .2, Vertical .2 Primary Header: Arial, Bold, 32pt. Bulleted List: Arial, 24pt. Single Spacing Limit text boxes to 9 inches width as maximum *Avoid orphans if possible. Break lines to prevent single words on a second line of a sentence. (target 4 to 6 bullets maximum per slide)
- One final complication that we should mention is Reye’s syndrome. This is a rare but severe syndrome that is almost exclusively seen in children and teenagers in association with a viral illness, most often influenza or varicella. The illness is characterized by fever and rash in the prodrome, followed by swelling of the liver and brain that leads to encephalopathy, liver failure, and often death. Supportive care is the only treatment. The exact cause of this deadly syndrome is still unknown, but there is thought to be an association with the use of aspirin. This has led the FDA to require warning labels on aspirin products in the US, instructing avoidance of this medication in children under age 18. Content Slide – Text only Logo: 1” high by 1.02” wide. Horizontal .2, Vertical .2 Primary Header: Arial, Bold, 32pt. Bulleted List: Arial, 24pt. Single Spacing Limit text boxes to 9 inches width as maximum *Avoid orphans if possible. Break lines to prevent single words on a second line of a sentence. (target 4 to 6 bullets maximum per slide)
- Credits Slide No Logo Header: Arial, 24pt, Content Area: Arial, 16pt. Slide Location in Bold.