Viral Pneumonia Cpirozzi

8/12/2019 Viral Pneumonia Cpirozzi

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Viral Pneumonia

Fellows conference

Cheryl Pirozzi, MDSeptember 7, 2011

oregonaidshotline.wordpress.com


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Viral Pneumonia

Epidemiology

General clinical features

Specific pathogens

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


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Viral pneumonia: Not just for kids!


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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):518-24

Marcos MA, Esperatti M, and Torres A. Viral pneumonia. Curr Opin Infect Dis 22:143147

Murray and Nadels Textbook of Respiratory Medicine 5thEdition


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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




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Risk factors for viral PNA in adults



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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 outcomecompared with bacterial PNA Viral PNA less likely to have lobar infiltrate (62% vs 84%)

and abnl WBC, almost all OctMay

Recommended routine isolation for all PNA pts.


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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



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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 PCRmethods



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Specific viral pathogens

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


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Case 1

75 yo woman (previously healthy) presents in December with2 days progressive f/c, dry cough, SOB, myalgias, and this CXR:

What is this most likely to be?


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Case 1



A) CMV PNA

B) Influenza

C) adenovirus

D) RSV

E) CHF


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Case 1



A) CMV PNA

B) Influenza

C) adenovirus

D) RSV

E) CHF


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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



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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

Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24Murray and Nadels Textbook of Respiratory Medicine 5

th

Edition

Ruuskanen et al. Viral pneumonia.

Lancet. 2011 Apr 9;377(9773):1264-

75


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Influenza

Influenza pandemics occur when new viruses are introducedinto the population

Historic pandemics of 1918 (H1N1- 50 million deaths

worldwide), 1957 (H1N1 and H2N2), 1968 (H3N2)

Avian influenza H5N11997 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%



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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%



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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)

Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15;42(4):518-24Murray and Nadels Textbook of Respiratory Medicine 5

th

Edition


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Influenza

Imaging

CXR may have bilateral reticulonodular infiltrates, sometimes

lower zone predominant



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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



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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 goodantigenic match

Live, attenuated vaccine

More effective in children

In adults equal or less effective than inactivated vaccine

Contraindicated in pregnant or immunosuppressed



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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



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Available treatment for influenza



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Case 2

Previously healthy 27 yo man with mild asthma p/w drycough, 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


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Case 2

Previously healthy 27 yo man with mild asthma p/w drycough, 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


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Respiratory syncytial virus (RSV)

2ndmost common cause of viral PNA in older adults

Common in winter (NovemberApril, 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 (2

nd

to influenza)Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181


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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 causebronchiolitis, bronchospasm, pneumonia, and acute

respiratory failure

Falsey A. Respiratory Syncytial Virus Infection in Adults. Semin Respir Crit Care Med. 2007;28(2):171-181


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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 chronicpulmonary disease or functional disability



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Influenza vs RSV



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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


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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 ribavirinIVIG and/or palivizumabis 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):171-181Shah et al. Blood. 2011;117(10):2755-2763


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Treatment of RSV

Prevention

Droplet precautions

No licensed RSV vaccination at this time; however, in

progress



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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



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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



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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, andimmunosuppressed, esp BMT pts



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Parainfluenza

Diagnosis

Ag or PCR in respiratory secretions or BAL

Treatment and prevention

aerosolized ribavirin has been used in children and BMTpts, but no trials showing efficacy

No vaccine



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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



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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


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

Top: 37-yo man

with bilateralpatchy GGO

without evidence

of fibrosis, with

random

distribution in

the transverseplane.

Bottom: 22-year-

old female SARS

patient with

random

distribution offibrosis, traction

bronchiectasis

(arrowheads), and

lung distortion,

with concomitant

GGO

SARS Imaging

Chest CT:

unilateral or

bilateral GGO,

interstitial

thickening, Mst

commonperipheral lower

lung zones


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Severe Acute Respiratory Syndrome (SARS)

Diagnosis

(PCR) detection in sputum, also blood and stool

Serum Abs (rise at 2-3 weeks)

Treatmentduring 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



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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



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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 ofinterstitial 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



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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

Murray and Nadels Textbook of Respiratory Medicine 5thEditionbjr.birjournals.org


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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



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Case 3

18 yo man p/w acute respiratory failure 10 days aftercleaning out a very dirty dusty cellar (including a nice

family of deer mice)

What might you be worried about?


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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


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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


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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, asymptomaticrespiratory 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 ARDSMurray and Nadels Textbook of Respiratory Medicine 5thEdition


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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 illpts 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.


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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



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Measles- clinical

Prodrome 2-8 days: fever, cough, anorexia,conjunctivitis, coryza, Kopliks spots

Then maculopapular erythematous rash

from face/necktrunkextremities

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 lethalgiant-cell PNA, incl pregnant, HIV pts (40%

mortality) and oncology pts (70%

mortality)


www.nlm.nih.gov/

http://missinglink.ucsf.edu


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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



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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



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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



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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



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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.



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Case 4

30 yo woman 30 wks pregnant p/w SOB, dry cough,

hemoptysis, hypoxia, and this funny rash:


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Case 4



And this CXR:


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Case 4



How should she be treated? A) supportive

B) high dose steroids

C) ribavirin

D) acyclovir

E) oseltamivir


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Case 4



How should she be treated? A) supportive

B) high dose steroids

C) ribavirin

D) acyclovir

E) oseltamivir


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Varicella-Zoster Virus (VZV)

Highly contagious herpesvirus

Incubation period 2 weeks

Varicella (chickenpox) outbreaks usually winter-

spring Respiratory tract infection leads to viremic

dissemination



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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, hemoptysisMurray and Nadels Textbook of Respiratory Medicine 5thEdition


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CXR: diffuse nodular infiltrates, which can resolve with miliarycalcific densities, also hilar adenopathy, pleural effusions,

peribronchial infiltrates



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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



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Characteristics of specific viral pathogens

Table

CID 2006:42



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Summary of antiviral treatment

Influenzaamantadine, oseltamivir RSVribavirin

Human metapneumovirussupportive

Parainfluenzasupportive

SARSsupportive (ribavirin and lopinavir unclear) CMVganciclovir

Hantavirusmaybe ribavirin

HSVacyclovir

Measlesvitamin A, maybe ribavirin

AdenovirusCidofovir

Rhinovirussupportive

Varicella-Zoster Virusacyclovir


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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 PNAthinkabout viral testing and isolation

Only some have effective antivirals


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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.


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.


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Available treatment for viral PNAs

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


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Viral Pneumonia Cpirozzi