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Viral Pneumonia

Viral Pneumonia. oregonaidshotline.wordpress.com. Fellows conference Cheryl Pirozzi, MD September 7, 2011. Viral Pneumonia. Epidemiology General clinical features Specific pathogens. http://www.armageddononline.org/viruses.html. Viral pneumonia: Not just for kids!. Viral Pneumonia.

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Viral Pneumonia

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  1. Viral Pneumonia oregonaidshotline.wordpress.com Fellows conference Cheryl Pirozzi, MD September 7, 2011

  2. Viral Pneumonia • Epidemiology • General clinical features • Specific pathogens http://www.armageddononline.org/viruses.html

  3. Viral pneumonia: Not just for kids!

  4. Viral Pneumonia • Viruses recently recognized as important pathogens in CAP due to improved diagnostic tests (PCR) • Cause of 2 - 35% of CAP in adults (more in kids) • Recent emergence of new viral respiratory pathogens Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143–147 Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24 Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  5. Risk factors for viral PNA in adults Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143–147 Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24 Elderly: Higher rates of hospitalization and death from viral PNA in persons >60 yo COPD and asthma: frequently complicated by respiratory viral infections Immunocompromised pts at increased risk

  6. Risk factors for viral PNA in adults Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  7. Who gets viral pneumonia? • Johnstone et al. Chest 2008;134;1141-1148 • 193 adults hospitalized with CAP, 47% with severe CAP, 15% viral and 4% mixed viral/bacterial • Patients with viral PNA were • older (76 vs 64), • more likely to have cardiac disease (66% vs 32%), • more frail (48% vs 21% limited ambulation) • Most common viruses: influenza, hMPV, and RSV • Similar presentations, no difference in outcome compared with bacterial PNA • Viral PNA less likely to have lobar infiltrate (62% vs 84%) and abnl WBC, almost all Oct – May • Recommended routine isolation for all PNA pts.

  8. Clinical syndromes • Upper respiratory tract (cold, pharyngitis, bronchitis) • Bronchiolitis: acute inflammatory disorder of small airways • obstruction with air trapping, hyperinflation, wheezing. • Most common < 2 yo • RSV most common, also human metapneumovirus, parainfluenza viruses, influenza A and B viruses, adenoviruses, measles virus, and rhinovirus • Pneumonia • Similar presentation to bacterial PNA Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  9. Diagnosis Nasal swab specimens, nasal aspirates, or combined nose and throat swab specimens. Sputum, endotracheal aspirate samples, or BAL Rapid antigen detection, viral culture and PCR methods Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  10. Specific viral pathogens Ruuskanen et al. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75

  11. Case 1 • 75 yo woman (previously healthy) presents in December with 2 days progressive f/c, dry cough, SOB, myalgias, and this CXR: • What is this most likely to be?

  12. Case 1 • 75 yo woman (previously healthy) presents in December with 2 days progressive f/c, dry cough, SOB, myalgias, and this CXR: • What is this most likely to be? • A) CMV PNA • B) Influenza • C) adenovirus • D) RSV • E) CHF

  13. Case 1 • 75 yo woman (previously healthy) presents in December with 2 days progressive f/c, dry cough, SOB, myalgias, and this CXR: • What is this most likely to be? • A) CMV PNA • B) Influenza • C) adenovirus • D) RSV • E) CHF

  14. Influenza • Most common cause of viral PNA in adults • family Orthomyxoviridae, Type A,B,C • 2 envelope glycoproteins, Antigenic variation in H and N leads to epidemic nature • Hemagglutinin (H) initiates infectivity- binds to cell • Neuraminidase (N) protein cleaves new virus allowing spread Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  15. Influenza • Annual winter epidemics x 6-8 wks (year round in tropics) • Transmitted by small particle aerosols • 2-3 day incubation period • Max virus shedding is at onset of illness, continues for 5 to 7 days Ruuskanen et al. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75 Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  16. Influenza • Influenza pandemics occur when new viruses are introduced into the population • Historic pandemics of 1918 (H1N1- 50 million deaths worldwide), 1957 (H1N1 and H2N2), 1968 (H3N2) • Avian influenza H5N1 – 1997 outbreak, 58% with PNA • Novel H1N1 influenza A virus emerged in Mexico and USA in Spring 2009 • High risk populations: infants, young kids, healthy adults 20-40s, pregnant/postpartum women, immunocompromised, obesity, DM, COPD, asthma • Elderly less susceptible to H1N1 due to prior exposure • Mortality in hospitalized pts 7% -17% Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  17. Influenza Each year, 300,000 hospitalizations (63% in >65 yo), and 36,000 deaths (85% in >65 yo) due to influenza 30% of pts hospitalized for influenza have CXR infiltrates secondary bacterial PNA in ? ~10% Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  18. Influenza Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition Clinical manifestations Acute onset fever, chills, dry cough, dyspnea, Pharyngeal pain, nasal congestion HA, myalgias, malaise, anorexia, GI sxs Altered mental status (more in older persons) Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  19. Influenza Imaging CXR may have bilateral reticulonodular infiltrates, sometimes lower zone predominant Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  20. Influenza • Secondary bacterial PNA • Mst common in elderly, or underlying pulm or cardiac dz • Period of improvement followed by increased cough, sputum production, and consolidation • Mst common Strep pneumo, then S. aureus and Grp A Strep Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  21. Treatment of Influenza Vaccines: • Inactivated virus vaccines: inactivated purified virions or partially purified HA and NA preparations • Efficacy 70% to 90% in healthy adults/children if good antigenic match • Live, attenuated vaccine • More effective in children • In adults equal or less effective than inactivated vaccine • Contraindicated in pregnant or immunosuppressed Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  22. Treatment of Influenza Antivirals • reduce severity and duration of illness • M2 inhibitors (M2Is) amantadine and rimantadine • Only influenza A • Neuraminidase inhibitors (NIs) oseltamivir and zanamivir • both influenza A and B Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  23. Available treatment for influenza Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  24. Case 2 • Previously healthy 27 yo man with mild asthma p/w dry cough, SOB, and wheezing, with O2 sats 80%/RA. The ER did this chest CT: • Nasal swab had + RSV PCR • How should he be treated? • A) high dose steroids • B) supportive care • C) inhaled ribavirin • D) IVIG

  25. Case 2 • Previously healthy 27 yo man with mild asthma p/w dry cough, SOB, and wheezing, with O2 sats 80%/RA. The ER did this chest CT: • Nasal swab had + RSV PCR • How should he be treated? • A) high dose steroids • B) supportive care • C) inhaled ribavirin • D) IVIG

  26. Respiratory syncytial virus (RSV) • 2nd most common cause of viral PNA in older adults • Common in winter (November – April, peak Jan-Feb) • Major cause of serious lower respiratory tract infections in young children • Primary RSV infection is nearly universal by age 2 and repeat infections are common due to incomplete immunity. • Also important pathogen in adults, esp elderly, chronic lung disease, or immunocompromised • Approx 10,000 deaths in persons > age 65 in the United States each year from RSV (2nd to influenza) Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181

  27. RSV- Pathogenesis • RSV is a single-stranded, enveloped RNA virus • Paramyxovirus family, A and B subtypes • Begins as upper respiratory tract infection, then can spread to lower respiratory tract and cause bronchiolitis, bronchospasm, pneumonia, and acute respiratory failure Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181

  28. RSV in adults Risk factors in adults • Immunocompromised patients (eg, severe combined immunodeficiency, leukemia, BMT or lung transplant) • Asthma • Other cardiopulmonary disease • Elderly, esp institutionalized or with chronic pulmonary disease or functional disability Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181

  29. Influenza vs RSV Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

  30. RSV: Imaging • CXR: diffuse bilat interstitial • CT: Bronchitis-bronchiolitis pattern: bronchial wall thickening and tree-in-bud opacities • Multifocal ground glass opacities or consolidation Miller W T , Shah R M AJR 2005;184:613-622

  31. RSV Testing • Culture: Not sensitive or specific in adults • Serologically: RSV-specific IgM or rise in IgG • Antigen detection by DFA or EIA • Sensitivity depends on specimen: nasal wash (15%), endotracheal secretions (71%), BAL (89%) • Reverse transcription-PCR (RT-PCR) • In adult nasal swabs: 73% sensitive and 99% specific • Recommendation: • Send nasopharyngeal swab for culture, + PCR if pt is severely ill / immunocompromised • Consider DFA if BAL or endotracheal specimen Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181 Falsey, Walsh. Clin Microbiol Rev. 2000 July; 13(3): 371–384.

  32. Treatment of RSV • Generally supportive: fluids, oxygen, and antipyretics • No data to support steroids or bronchodilators • Ribavirin (aerosolized, IV, PO) • IVIG or RSV-IVIG • Immunomodulators: Palivizumab (PVZ) • RSV-specific monoclonal Ab • Treatment with ribavirin ± IVIG and/or palivizumab is indicated in BMT or transplant pts, but there is insufficient data to support treating healthy adults Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181 Shah et al. Blood. 2011;117(10):2755-2763

  33. Treatment of RSV • Prevention • Droplet precautions • No licensed RSV vaccination at this time; however, in progress Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181

  34. Human metapneumovirus (hMPV) • Paramyxovirus, closely related to RSV • Common in children, but also common cause of PNA in immunocompromised and elderly adults • Often coinfection with RSV and other resp viruses • Droplet transmission • Winter outbreaks Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  35. Human metapneumovirus (hMPV) • Clinical: ranges from mild URI to severe bronchiolitis and pneumonia • In general similar presentation to RSV, though less severe • Diagnosis: PCR most sensitive, also serology and culture • Treatment: • Supportive • No effective antivirals or vaccines, though ribavirin has in vitro activity and has been used Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  36. Parainfluenza • Paramyxovirus RNA virus • Outbreaks fall-spring, every 2-3 yrs • Direct contact by respiratory secretions or large aerosols • Incubation 3-6 days • Common cause of croup, bronchiolitis, or PNA in kids, but can also cause PNA in adults, elderly, and immunosuppressed, esp BMT pts Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  37. Parainfluenza • Diagnosis • Ag or PCR in respiratory secretions or BAL • Treatment and prevention • aerosolized ribavirin has been used in children and BMT pts, but no trials showing efficacy • No vaccine Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  38. Coronaviruses • Enveloped RNA viruses • Frequent cause of common cold • 4-15% of acute respiratory disease in adults, but rarely PNA • Most common winter and early spring, outbreaks q. 2-3 yrs • Incubation period 3 to 4 days Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  39. Severe Acute Respiratory Syndrome (SARS) • HuCoV-SARS: group II coronovirus • emerged in southern China in spring 2003 and rapidly spread worldwide. • incubation period 2 to 10 days • Clinical presentation: • Cough and dyspnea, fever, chills /rigors, myalgias, diarrhea • 20% of patients required respiratory support. • Mortality 11% for all ages but much higher in older adults • Some developed pulmonary fibrosis after acute illness • Pathology: diffuse alveolar damage bryanking.net Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  40. SARS Imaging • Chest CT: unilateral or bilateral GGO, interstitial thickening, Mst common peripheral lower lung zones Top: 37-yo man with bilateral patchy GGO without evidence of fibrosis, with random distribution in the transverse plane. Bottom: 22-year-old female SARS patient with random distribution of fibrosis, traction bronchiectasis (arrowheads), and lung distortion, with concomitant GGO Hsu H et al. Chest 2004;126:149-158

  41. Severe Acute Respiratory Syndrome (SARS) • Diagnosis • (PCR) detection in sputum, also blood and stool • Serum Abs (rise at 2-3 weeks) • Treatment – during the outbreak, treatment with: • ribavirin, protease inhibitors (lopinavir/ritonavir) • High dose steroids • type I interferons, chloroquine (unclear mechanism) • In retrospect unclear that any were effective, recommended treatment is supportive Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  42. Cytomegalovirus (CMV) • gammaherpesvirus subfamily of the herpesviruses • Transmitted through direct contact • Virus excreted in urine, saliva, stool, tears, breast milk, vaginal secretions, and semen • No seasonal patterns Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  43. Cytomegalovirus (CMV) • In immunocompetent persons, most infections are subclinical: can cause pharyngitis, rarely PNA • In immunocompromised, important cause of PNA • In BMT pts, mst common infectious cause of interstitial PNA, with high mortality • Greatest risk of CMV PNA 30-90 days after BMT • Lung transplant recipients: can cause PNA, pneumonitis, and lead to bronchiolitis obliterans Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  44. Cytomegalovirus (CMV) • Clinical: fever, nonproductive cough, dyspnea, Crackles, tachypnea, hypoxemia • May have mild neutropenia, thrombocytopenia, and elevated liver enzymes • Imaging: bilat diffuse miliary or interstitial infiltrates, middle and lower lung fields • On CT small nodules, consolidation, and GGOs • Path: eosinophilic intranuclear viral inclusions bjr.birjournals.org Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  45. Cytomegalovirus (CMV) • Treatment: PNA is difficult to treat • Ganciclovir and IV CMV immune globulin reduces mortality from approx 90% to 50% • Cidofovir and foscarnet unclear efficacy • Prevention in high risk pts • No vaccines • CMV-Seronegative BMT pts should only get leukocyte reduced/CMV-seroneg blood products • In CMV mismatched solid organ transplant recipients, posttransplant prophylaxis with ganciclovir Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  46. Case 3 • 18 yo man p/w acute respiratory failure 10 days after cleaning out a very dirty dusty cellar (including a nice family of deer mice) • What might you be worried about?

  47. Hantavirus • Bunyavirus family, single strand RNA virus • Many different viruses associated with different rodent hosts • Sin Nombre Virus (SNV) associated with deer mouse • Transmission by contact with infected rodent poop (infectious for 150 days post-rodent infection!) • No person-person, except possibly in one outbreak in South America • Incubation 8-20 days • SW outbreak in 1993 forces.si.edu Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  48. Hantavirus • Severe, often fatal PNA • Clinical: f/c, myalgias, GI sxs, then after a few days progressive nonproductive cough, dyspnea • Pathogenesis: capillary leak and noncardiogenic pulmonary edema • Labs: thrombocytopenia, left shift with circulating myeloblasts, mildly elevated LFTs • CXR: bilateral infiltrates c/w ARDS • Mortality 30-40% • Also causes cardiopulmonary and hemorrhagic fever with renal disease syndrome cdc.gov Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  49. Hantavirus • Diagnosis •  Hantavirus IgM and IgG at time of presentation • Serum PCR • Treatment: • Supportive • High dose steroids, ECMO possibly effective • Ribavirin effective in vitro, no good trials showing efficacy Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

  50. Herpes Simplex Viruses (HSV) • HSV-1 most associated with respiratory disease • Transmitted by respiratory secretions, vesicle fluid on close contact • 30-100% of adults are seropositive, asymptomatic respiratory shedding in 1-2% of seropositive adults • Cause of PNA in neonates, and in severely immunocompromised adults esp on mechanical ventilation, eg malignancy, burns, transplant pts • Extension of infection from tracheobronchial tree to the lung or hematogenous dissemination • Associated with ARDS Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

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