viral pneumonia fellows conference cheryl pirozzi, md september 7, 2011...

Viral PneumoniaFellows conferenceCheryl Pirozzi, MDSeptember 7, 2011

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Viral Pneumonia

• Epidemiology• General clinical features• Specific pathogens

http://www.armageddononline.org/viruses.html

Viral pneumonia: Not just for kids!

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

Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143–147

Murray and Nadel’s Textbook of Respiratory Medicine 5th Edition

Risk factors for viral PNA in adults

• 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

Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143–147Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24

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

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.

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


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


Specific viral pathogens

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

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?

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


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




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%


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%


Influenza

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)



Influenza

Imaging• CXR may have bilateral reticulonodular infiltrates, sometimes

lower zone predominant


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


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


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


Available treatment for influenza


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

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

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

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


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


Influenza vs RSV


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

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, Walsh. Clin Microbiol Rev. 2000 July; 13(3): 371–384.Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181

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


Shah et al. Blood. 2011;117(10):2755-2763

Treatment of RSV

• Prevention– Droplet precautions– No licensed RSV vaccination at this time; however, in

progress


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


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


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


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


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


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

Hsu H et al. Chest 2004;126:149-158

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

SARS Imaging

• Chest CT: unilateral or bilateral GGO, interstitial thickening, Mst common peripheral lower lung zones

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


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



• 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



• 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


• 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


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?

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

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

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


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


Herpes Simplex Viruses (HSV)

• Can cause focal PNA or diffuse interstitial PNA• CT: multifocal GGOs, nonspecific• Diagnosis

– Frequently found in BAL (by PCR or culture) of critically ill pts due to spread/aspiration from oropharynx, but unclear if true pathogen

• Treatment– IV acyclovir, alternative foscarnet– Inconsistent data to support effectiveness of antiviral

treatment on the outcome of critically-ill patients


Simoons-Smit et al.Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clin Microbiol Infect. 2006 Nov;12(11):1050-9.

Measles

• Uncommon here due to vaccination, but in resource-poor countries (and damn hippies) can cause fatal PNA

• Morbillivirus genus of the Paramyxoviridae family• Epidemics q. 2-5 yrs• Airborne transmission, highly contagious• Incubation 9-14 days• Mortality 0.1% in developed coutries, 2-25% in

developing countries, due to respiratory or neurologic dz


Measles- clinical

• Prodrome 2-8 days: fever, cough, anorexia, conjunctivitis, coryza, Koplik’s spots

• Then maculopapular erythematous rash from face/neck trunk extremities

• Few days after rash appears, defervescence and sx improvement

• Lower respiratory tract involvement in 4-50% with bronchitis, PNA, or bronchiolitis

• In immunocompromised, can cause lethal giant-cell PNA, incl pregnant, HIV pts (40% mortality) and oncology pts (70% mortality)


www.nlm.nih.gov/

http://missinglink.ucsf.edu

Measles- clinical

• CXR: multilobar reticulonodular infiltrate• Secondary bacterial infection in 30% to 50%

– Haemophilus influenzae, Neisseria meningitidis, and S. pneumoniae

• Other complications: hepatitis, encephalitis, keratitis, mesenteric adenitis, severe diarrhea


Measles

• Diagnosis: – respiratory secretions or urine show multinucleated giant

cells, + immunoflourescent staining

• Prevention:– live attenuated virus = >90% durable immunity

• Treatment:– Supportive care– Vitamin A improves mortality and recovery time– Ribavirin in vitro activity, but no proven clinical efficacy


Adenovirus

• Nonenveloped DNA viruses• Common cause of pharyngitis, tracheitis, and bronchitis• Rare cause of pneumonia in adults and children

– Clinical characteristics similar to those of other pneumonias

• In transplant patients and other immunosuppressed pts can cause fatal pneumonia and disseminated infection, with hepatitis, hemorrhagic cystitis, and renal failure


Adenovirus

Treatment and prevention• No proven antiviral treatment• Cidofovir has the most in vitro activity and has been used with

some success in seriously ill and/or immunocompromised patients (case reports, no RCTs)

• Effective live oral vaccines were developed for military, but are no longer produced


Rhinovirus

• The most common cause of URIs, sinusitis, OM, and bronchitis

• Causes PNA and bronchiolitis in infants and severe PNA in adult transplant and oncology pts

• Diagnosis: culture, rapid Ag or PCR tests• Treatment: symptomatic

– Pleconaril? – not currently available.


Case 4

• 30 yo woman 30 wks pregnant p/w SOB, dry cough, hemoptysis, hypoxia, and this funny rash:

Case 4


• And this CXR:

Case 4


• How should she be treated?– A) supportive– B) high dose steroids– C) ribavirin– D) acyclovir– E) oseltamivir

Varicella-Zoster Virus (VZV)

• Highly contagious herpesvirus• Incubation period 2 weeks• Varicella (chickenpox) outbreaks usually winter-

spring• Respiratory tract infection leads to viremic

dissemination



Clinical• Usually fever, malaise, or pharyngitis, then rash from head to

trunk/extremities (lesions in various stages) • VZV PNA in 1/400 cases, with 10-30% mortality• In immunocompromised children and adults, more severe

course with high fevers, PNA , meningoencephalitis, hepatitis• Severe PNA in 10% of varicella infections during pregnancy• PNA can occur in healthy adults (25x more frequently than kids)

– Smoking is RF

• Sxs usually 1-6 d after rash onset• Cough, dyspnea, pleuritic CP, hemoptysis



• CXR: diffuse nodular infiltrates, which can resolve with miliary calcific densities, also hilar adenopathy, pleural effusions, peribronchial infiltrates



• Diagnosis– Clinical (rash + PNA)– Lesion scrapings (Tzank smear) sensitivity 70% to 85% – Direct immunofluorescence for VZV antigen in lesions– BAL PCR

• Treatment– IV acyclovir x 5-7 days is effective– Steroids controversial; no good data

• Prevention– Live, attenuated varicella vaccine 50-90% effective


Characteristics of specific viral pathogens

• Table• CID 2006:42


Summary of antiviral treatment• Influenza – amantadine, oseltamivir• RSV – ribavirin• Human metapneumovirus – supportive• Parainfluenza – supportive • SARS – supportive (ribavirin and lopinavir unclear)• CMV – ganciclovir • Hantavirus – maybe ribavirin• HSV – acyclovir• Measles – vitamin A, maybe ribavirin• Adenovirus – Cidofovir • Rhinovirus – supportive • Varicella-Zoster Virus – acyclovir

Conclusions

• Viral PNA is a big deal for adults too, especially elderly and immunocompromised

• Clinical presentation of viral PNAs are similar to each other and to bacterial PNA – think about viral testing and isolation

• Only some have effective antivirals

References• Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-

acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008 Dec;134(6):1141-8. Epub 2008 Aug 8

• Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24. Epub 2006 Jan 6.

• Jordi Rello and Aurora Pop-Vicas. Clinical review: Primary influenza viral pneumonia. Crit Care. 2009; 13(6): 235.

• Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit Care Med. 2010 Apr;38(4 Suppl):e91-7.

• Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75. Epub 2011 Mar 22.

• Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143–147• Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181• Shah J, Chemaly R. Management of RSV infections in adult recipients of hematopoietic stem cell

transplantation. Blood. 2011;117(10):2755-2763• Hsu et al. Correlation of HRCT, symptoms, and pulmonary function in patients during recovery from Severe

Acute Respiratory Syndrome. Chest 2004; 126:149-158• Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel RJ, Vandenbroucke-Grauls CM.Herpes simplex

virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clin Microbiol Infect. 2006 Nov;12(11):1050-9.

Available treatment for viral PNAs


viral pneumonia fellows conference cheryl pirozzi, md september 7, 2011...

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