Viral pneumonia

Dr George Mothi Justin

Consultant Pulmonologist

Medical trust Hospital

Previously healthy 54yr old lady was referred from a local hospital Progressive respiratory failure Following a febrile illness x 2-3 days Admitted to the ICU in respiratory distress

Blood counts were normal Mild renal failure Started on

Antiviral (Oseltamivir – 150 mg twice daily) & I/V broad-spectrum antibiotics

Supplemental high flow oxygen Blood culture & urine culture -negative ABG’s s/o ARDS Intubated & mechanically ventilated

Weaned & extubated on Day 7

Clinical & radiological improvement

Viral Pneumonia

Pneumonia is syndrome caused by acute infection, usually bacterial, characterized by clinical and/or radiographic signs of consolidation of a part or parts of one or both lungs

Viral pneumonias – when viruses are aetiological agents

WHY HAS VIRAL PNEUMONIAS BECOME IMPORTANT?

Incidence of viral pneumonia has increased during the past decade

Increase in population of at-risk groups & patients who are immunocompromised

Emergence of Severe acute respiratory syndrome (SARS), Avian influenza A (H5N1) virus, 2009 pandemic influenza A (H1N1) virus

Discovery of new respiratory viruses Human metapneumovirus Coronaviruses - NL63 and HKU1

Hantavirus Human bocavirus

Availability of molecular diagnostic assays (such as PCR)

Etiology

Adenoviridae (adenoviruses) Coronaviridae (coronaviruses) Bunyaviridae (arboviruses) -Hantavirus Orthomyxoviridae (orthomyxoviruses) - Influenza

virus Papovaviridae (polyomavirus) – JC virus, BK virus Paramyxoviridae (paramyxoviruses) -Parainfluenza

virus (PIV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), measles virus

Picornaviridae (picornaviruses) – Enteroviruses, coxsackievirus, echovirus, enterovirus 71, rhinovirus

Reoviridae (rotavirus) Retroviridae (retroviruses)- HIV , human

lymphotropic virus type 1 (HTLV-1)

Immunocompetent Host

Influenza virus Respiratory syncitial Virus (RSV) Parainfluenza virus (PIV) Adenovirus Measles Varicella Zoster virus

Immunocompromised Host

Cytomegalovirus (CMV) Herpes Simplex Virus (HSV) Varicella Zoster Virus (VZV) Adenoviruses Respiratory syncitial Virus (RSV) Parainfluenza Virus Rhinovirus Measles- Giant cell pneumonia

Emerging Viruses

Hantavirus Pulmonary Syndrome SARS Associated with significant mortality

Brief discussion

Viral pneumonia Mild and self-limited illness to a Life-threatening disease

Four Most commom viruses encountered1. Influenza virus2. Respiratory syncytial virus (RSV)3. Adenovirus4. Parainfluenza virus

Influenza virus types A and B are responsible for more than half of all community-acquired viral pneumonia cases

Outbreaks of adenovirus of various serotypes frequently occur in military recruits

Adenovirus type 14 (Ad 14), a new variant in the United States, has been shown to cause severe and sometimes fatal acute respiratory illness

Viruses cause 13-50% of pathogen-diagnosed community-acquired pneumonia

8-27% of cases are mixed bacteria-virus

RSV 1-4%, adenovirus 1-4%, PIV 2-3 %, hMPV 0-4%, coronavirus 1-14% of pathogen-diagnosed pneumonia

Influenza is high in elderly persons

63% of the 300,000 influenza-related hospitalizations and 85% of 36,000 influenza-related deaths occur in patients aged 65 years or older

RSV is the most common etiology of viral pneumonia in infants and children and second most common viruses in elderly

Parainfluenza infection is the second most common viral illness in infants

Adenovirus accounts for 10% of pneumonias in children

Viral pneumonia in pregnancy often underdiagnosed

Influenza virus, VZV, and measles virus most common viruses in pregnancy

Infection Acute respiratory decompensation/ Respiratory failure/ARDS maternofetal hypoxia, preterm labor, multisystem organ failure, and even death

Influenza pneumonia & VZV pneumonia lethal with mortality rates of 35-40% in pregnant women, compared with 10% in the general population.

Pregnant women with viral pneumonia have a higher risk for severe disease than other females

Viral Pneumonia in Pregnancy

Men who are infected develop viral pneumonia at a slightly higher rate than women

Most viruses that can cause pneumonia generally infect children and cause a mild illness; healthy adults also develop mild disease

Elderly persons and persons who are immunosuppressed develop severe viral pneumonia

2009-2010 H1N1 influenza pandemic - infection was more common in the population aged 5-59 years than in the elderly

Reason could be lack of exposure and thus immunity, to the 1957 (and earlier) H1N1 influenza strain

Antigenic Shift vs Drift

Antigenic drift is a gradual continuous ongoing process that results in the emergence of new strain variants.

Antigenic shift is a sudden abrupt change in the antigen by which an novel strain of virus is evolved which acquires the capability of infecting human beings Usually associated with pandemics

Pathophysiology

Respiratory viruses multiply in the epithelium of the upper airway and secondarily infect the lung by means of airway secretions or hematogenous spread

Severe pneumonias may result in extensive consolidation of the lungs with varying degrees of hemorrhage

The mechanism of damage to tissues 1. Cytopathic2. Over exuberant inflammation

Immune responses 1. Type 1 cytokines - promote cell-mediated

immunity2. Type 2 cytokines - mediate allergic responses.

Cell-mediated immunity appears to be important for recovery from certain respiratory viral infections

Impaired type 1 response may explain why immunocompromised patients have more severe viral pneumonias

Figure 1. Photomicrograph (original magnification, ×100; hematoxylin-eosin stain) of a lung biopsy specimen from a 36-year-old man with pneumonia due to herpes simplex virus type 1

shows a fibrous exudate (large arrows) along the alveolar walls.

Kim E A et al. Radiographics 2002;22:S137-S149

©2002 by Radiological Society of North America

Respiratory viruses damage the respiratory tract and stimulate the host to release multiple humoral factors, including histamine, leukotriene C4, and virus-specific immunoglobulin E bradykinin, interleukin 1, interleukin 6, and interleukin 8

RSV infections can alter bacterial colonization patterns, increase bacterial adherence to respiratory epithelium, reduce mucociliary clearance, and alter bacterial phagocytosis by host cells.

Transmission

Diagnosis of Viral Pneumonia

History Fever, myalgia, malaise Upper respiratory symptoms Cough (with or without sputum production) Tachypnea and/or dyspnea Tachycardia or bradycardia Wheezing Rhonchi Rales

Sternal or intercostal retractions Dullness to percussion Decreased breath sounds Pleurisy Friction rub Hypoxia, Cyanosis Acute respiratory distress syndrome

Influenza Pneumonia Especially affects

Children with cystic fibrosis or transplants Adults with chronic cardiovascular or respiratory

disease, diabetes mellitus, renal diseases, hemoglobinopathies, or immunosuppression Residents of nursing homes or chronic care

facilities Healthy adults older than 65 years.

Influenza Pneumonia

The 3 clinical forms of influenza pneumonia are primary influenza pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonia

Laboratory diagnosis of viral pneumonia

Detection of virus or viral antigen in upper-respiratory secretions by culture or immunofluorescence microscopy

Measurement of antibodies in paired serum samples.

PCR has increased the ability to detect respiratory viruses

ARE THESE SIMPLE and ACCURATE TESTS?

Specimens from the lower-respiratory tract can be hard to obtain

Distinguishing prolonged shedding from colonization can be difficult

Detection of a virus in the nasopharynx could represent coincidental upper-respiratory infection or a pneumonia pathogen.

Viral cultures are still the criterion standard for most viral pathogens, but they take a long time to complete

Viral-antigen detection is one of the new tests, but the results are generally less sensitive and less specific than those of conventional cell cultures

PCR-based tests with single, multiplex, and real-time readings have sensitivity better than that of cultures

Cytologic Evaluation

Types of specimen required

Respiratory secretions- nasopharyngeal swabs or wash Bronchoalveolar lavage samples

Tissue specimens

Intranuclear inclusions often exist in cells infected with DNA viruses

Cytoplasmic inclusions usually are present in cells infected with RNA viruses

CMV infection characteristically is associated with "owl's-eye" cells, which are large cells with basophilic intranuclear inclusions and a surrounding clear zone.

The presence of viral inclusions is diagnostic, although this method has low sensitivity

Viral Culture Used for isolation and identification of the pathogen

Tissue used for culture1. sputum samples2. nasopharyngeal washing3. bronchoalveolar lavage4. biopsy

Viral transport medium -consists of enriched broth containing antibiotics and a protein substrate

The cultures - examined for cytopathogenic effects and for evidence of viral growth

Viral growth - detected through hemadsorption testing by demonstrating adherence of red blood cells to the cultured cell monolayer of infected tissue

Further identification of viruses is accomplished using immunofluorescence

Viral cultures are of lower yield in RSV infection, human metapneumo virus infection and coronavirus infection

Modified cell culture methods called shell vial culture systems are able to detect certain slow-growing viruses

Shell vial culture systems are used widely for earlier detection of CMV, RSV, herpes simplex virus (HSV), adenovirus, influenza viruses, parainfluenza virus (PIV), and other viral pathogens

Rapid Antigen Detection

Provide faster results

Nasal swabs or washings are easy to obtain

Immunofluorescence assay and enzyme-linked immunosorbent assay (ELISA) – for the diagnosis of HSV, RSV, influenza viruses A and B,

PIV, CMV, and other respiratory viruses

ELISA can detect viral antigens, while an immunofluorescence assay requires the presence of prepared, intact, infected cells

Advantages

Higher specificity for individual viruses

Assays remain positive for several days to weeks, long after the culture technique can detect viable virus

Disadvantages

The overall sensitivity is lower than that of viral cultures

Antigen detection methods should be used in conjunction with cell culture

RSV rapid antigen detection is useful in young children, who shed high titers of virus, but sensitivity is low in adults (0-20%) when compared with RT-PCR.

Sensitivity for seasonal influenza in adults ranges between 50% and 60%, and specificity is greater than 90%.

Gene Amplification

PCR is a highly sensitive and specific technique for amplifying genes to detect the presence of a virus

For many viruses, this is the diagnostic test of choice

Used in combination with viral culture and immunocytologic and rapid antigen detection

PCR technology allowed the discovery of such viruses as RSV, hMPV, and coronaviruses in causing pneumonias.

For influenza H1N1 and avian influenza, RT-PCR of either nasopharyngeal swabs or bronchial aspirates/sputa is the diagnostic modality of choice.

PCR has become especially useful for the detection of CMV in various body fluids (eg, blood, urine) in severely immunocompromised patients, particularly hematopoietic stem cell transplant (HSCT) recipients.

Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR), permits rapid detection of influenza virus types A and B, RSV (types A and B), adenoviruses, PIV (types 1, 2, and 3), hMPV, and rhinovirus

The single-step MRT-PCR technique has high sensitivity and specificity.

Serologies

Measured by

1. Complement fixation

2. Enzyme immunoassay [EIA]

This method ideally requires a 4-fold rise in titers.

Requires blood to be drawn in the convalescent phase

It is not as useful in the acute management of the patient

Serologies are particularly useful for definitively confirming the diagnosis, especially the positive results of other diagnostic tests.

Other tests

White-blood-cell count C-reactive protein and procalcitonin

Above biomarkers are raised in individuals with bacterial pneumonia compared with patients with viral pneumonia

Levels of procalcitonin -increases within 6–12 h after onset of bacterial infection and

halves daily when infection is controlled

Procalcitonin greater than 0·5 μg/L support bacterial infection, whereas repeatedly low amounts suggest that bacterial infection is unlikely.

Chest X-ray

Bilateral lung involvement

Influenza -Perihilar and peribronchial infiltrates

Progression to diffuse interstitial infiltrates is observed with severe disease.

Avian influenza pneumonia –

patchy, interstitial, and/or diffuse infiltrates, consolidation, pleural effusion, and pneumothorax

RSV pneumonia -patchy bilateral alveolar infiltrates and interstitial changes

Adenovirus pneumonia-, bilateral and patchy, ground-glass infiltrates with a preference for lower lobes

PIV pneumonia-diffuse interstitial infiltrates or diffuse mixed alveolar-interstitial infiltrates

hMPV pneumonia-bilateral, interstitial, and alveolar infiltration in 43% and unilateral infiltration in 57%

Coronavirus pneumonia- Ground-glass opacities and focal consolidations, especially in the periphery and subpleural regions of the lower zones

VZV pneumonia- Diffuse, fluffy, reticular or nodular infiltrates that can be rapidly progressive. Pleural effusion and peripheral adenopathy

CMV pneumonia- 2 patterns (1) multifocal or miliary pattern (2) Diffuse interstitial pneumonitis with interstitial

edema

HSV pneumonia-small centrilobular nodules and patchy ground-glass opacities and consolidation

Hantavirus pneumonia-normal chest radiograph during early disease followed by signs of interstitial edema, Kerley B lines, peribronchial cuffing, and indistinct hila

Diagnostic Techniques Used for Viral Pneumonia

Treatment and Prevention

Oseltamivir

Dosage Recommendation Adults 75-mg capsule twice per day

150mg twice daily in severe forms of the disease

Oseltamivir or Zanamivir for treatment of all hospitalized patients with

suspected or confirmed cases for outpatients at increased risk for complications

of H1N1 infection

Peramivir

IV Peramivir was approved for patients not responded to either oral or inhaled

antiviral therapy and/or drug delivery by a route other than IV that

was not expected to be dependable or feasible

Virus Treatment Prevention

Influenza Vaccines Two types

Trivalent Inactivated Vaccine (TIV) – intramuscular Live attenuated (CAIV)- intranasal

High-risk groups- Age<5yrs>50yrs C/c heart/lung disease Immunosuppressed Pregnancy Health care workers

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