Your Family Physician

Sunday, May 3, 2009

Pneumonia, Viral

Introduction

Background

Viruses account for the largest proportion of childhood pneumonia; viruses decrease in frequency as the etiology of pneumonia in healthy adults, and once again become frequent causes of death and morbidity in persons older than 60 years.

Viral pneumonia is a subset of the pneumonitides, which were at one time called atypical pneumonias. In the past, all pneumonias were labeled atypical if a bacterial pathogen could not be identified with Gram staining and if the pneumonia did not respond to antibiotics. A number of rapid tests to determine viral etiologies have now been developed. Their use in the emergency department (ED) has allowed bedside diagnosis of the etiology of viral pneumonia. This testing is important for both epidemiologic surveillance and treatment because many viral pneumonias have overlapping clinical presentations with each other and bacterial pneumonia, making diagnosis on purely clinical grounds difficult or impossible.

Viral pneumonia can vary from a mild illness to a life-threatening disease with respiratory failure, severe hypoxemia, and other pulmonary pathology. Severe acute respiratory syndrome (SARS) was a recent example of a viral illness associated with high mortality and morbidity secondary to overwhelming pneumonia and pulmonary complications. The spread of disease was controlled with classic techniques of isolation of sick patients and contacts. Currently, the possibility of a pandemic due to an avian influenza virus labeled A/H5N1 is a grave concern. This virus has been spreading from Southern China to other parts of the world, mainly via poultry-to-human transmission, but sporadic cases of human-to-human transmission have occurred. Illness results in overwhelming pulmonary disease and a high mortality rate.

The viral pneumonias impose a heavy burden on society because of morbidity and occasionally high rates of mortality, depending on the virulence of the organism as well as age and comorbidities of the patients. The cost of treating patients, preventing and controlling outbreaks, and attempting to prevent pandemics is also a burden.

The most common viral agents resulting in pneumonia were influenza A; respiratory syncytial virus (RSV); and parainfluenza 1, 2, and 3. Multiple viral pathogens are often identified. The most common viral agents resulting in pneumonia were influenza A; respiratory syncytial virus (RSV); parainfluenza 1, 2, and 3; and adenovirus. 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 in patients of all ages but especially the young, the old, patients with underlying comorbid conditions, and those who are immunocompromised.

Studies show that patients are frequently infected with both bacterial and viral pathogens, making it impossible to rule out bacterial disease even when rapid viral test results are positive. Additionally, no unique identifying clinical characteristics are present that allow the physician to differentiate viral disease from bacterial disease in the ED.

Viruses are divided into categories depending on whether the pneumonia they cause is a primary manifestation or part of a multisystem syndrome of disease. Those that cause pneumonia as a primary manifestation of disease include influenza virus types A and B, RSV, adenovirus, parainfluenza virus, rhinovirus, Hantavirus, and cytomegalovirus (CMV). Those that cause pneumonia as part of a multisystem syndrome include Paramyxovirus species (measles), varicella-zoster virus, Epstein-Barr virus, CMV, and herpes simplex virus.

Viral pathogens can be the etiology of community-acquired pneumonia. Although the most common cause of community-acquired pneumonia remains Streptococcus pneumoniae (a fact that may change with the increasing use of pneumococcal vaccines), in as many as 40-60% of patients with community-acquired pneumonia, the etiologic agent is not identified. Furthermore, convincing associations between the patient's symptoms, physical findings, laboratory test results, and specific etiologies are lacking. Therefore, no way of accurately determining the etiology of pneumonia during the initial visit to the ED exists. Obtaining a chest radiograph in patients with suspected pneumonia is recommended, both to find complications, such as pleural effusions, and to discourage the use of antibiotics in healthy patients with bronchitis rather than pneumonia.

Pathophysiology

Epidemiology

Viral pathogens account for 1-23% of community-acquired pneumonias in adults, with influenza virus being the most common agent. Overall, the most common cause of community-acquired pneumonia remains S pneumoniae. Furthermore, convincing associations between individual symptoms, physical findings, and specific etiologies are lacking so that firm diagnosis of the agent, whether bacterial or viral, depends on laboratory testing. Fortunately, bedside testing is now available.

The route of spread of viruses depends on the type of virus involved. Routes include large-droplet spread over short distances (<1>1 Pneumonia is a common complication of influenza.

Influenza viruses have segmented RNA genomes and are classified as type A, B, or C. Influenza type A is usually the most virulent pathogen. The influenza virus has 2 envelope glycoproteins, hemagglutinin (H) and neuraminidase (N), which are important for a number of reasons. The hemagglutinin initiates infectivity by binding to cellular sialic acid residues, whereas the N protein cleaves newly synthesized virus from sialic acid on cell surfaces, thus allowing spread of the virus to other cells. The influenza virus maintains its infectivity by undergoing antigenic drift (small number of amino acid substitutions) and shift (large number of amino acid substitutions) due to changes in the protein structure of the surface protein, hemagglutinin. Epidemics occur when a viral drift occurs, and pandemics are seen with viral shift (two influenza A viruses exchange H or N genes during infection of the same hosts) because most people have no prior immunity to the virus. These 2 envelope proteins are important targets of neutralizing antibody.2

H1N1 swine flu

April 27, 2009. On April 26th, the US Department of Health and Human Services issued a nationwide public health emergency regarding human cases of swine influenza A (H1N1) virus.3 In the past several weeks, there has been an outbreak of the virus in Mexico (~1600 cases) and the United States (40 cases, according to the CDC as on 1 PM, April 27) caused by a new strain of influenza virus that contains a combination of swine, avian, and human influenza virus genes. In Mexico, 103 deaths are suspected to be caused by the recent swine influenza outbreak. Cases of the virus have been confirmed in patients in California (7), Kansas (2), New York City (28), Ohio (1), and Texas (2). No deaths from the virus have been confirmed in the United States.4 Internationally, confirmed cases have also been reported in Canada, New Zealand, Spain, and the United Kingdom (Scotland), with suspected cases in Brazil, Israel, and France.5

If swine flu is suspected, clinicians should obtain a respiratory swab for swine influenza testing and place it in a refrigerator (not a freezer). Once collected, the clinician should contact their state or local health department to facilitate transport and timely diagnosis at a state public health laboratory.6

The new virus is resistant to the antiviral agents amantadine and rimantadine but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). Initiation of antiviral agents within 48 hours of symptom onset is imperative to provide treatment efficacy against influenza virus. The usual vaccine for influenza administered at the beginning of the flu season is not effective for this viral strain.

Initial symptoms of swine influenza include high fever, myalgias, rhinorrhea, and sore throat. Nausea, diarrhea, and vomiting have also been reported. Infection control precautions (ie, handwashing, covering mouth with tissue when sneezing or coughing) are encouraged. If suspected swine flu occurs, isolation is recommended for infected individuals and household contacts. For more information, see updated information from the US Centers for Disease Control and Prevention.

Avian flu

Concern is growing that avian influenza, which is a subtype of influenza A, may result in a worldwide pandemic in the near future. This subtype of influenza causes high mortality as a result of pneumonia and respiratory failure. In 1997, 18 cases of human infection were documented with 6 fatalities. The outbreak was thought to be controlled by depopulating 1.5 million chickens in Hong Kong farms and markets. However, human infections have occurred in 2001, 2002, and 2003 in other parts of Asia, and there are reports of the virus being found in poultry and birds in Europe.

The avian influenza virus A/H5N1 has several ominous characteristics, including increased virulence and human-to-human transmission in several cases, rather than bird-to-human transmission, as is usually necessary. In the 1997 Hong Kong outbreak of 18 patients, 11 were younger than 14 years. Seven of the patients recovered, but 11 patients progressed to pneumonia. Of the 11 patients with pneumonia, 6 died from acute respiratory distress syndrome (ARDS) or multisystem organ failure. Reye syndrome and pulmonary hemorrhage were also complications. Significantly, 8 patients treated with amantadine did not have confirmed benefit from treatment. Worldwide, more than 200 human cases of avian influenza from A/H5N1 or subtypes A/H5, A/H7, and A/H9 have been reported, with greater than 50% mortality in those infected with A/H5N1.7

SARS is due to a novel coronavirus (CoV) first identified in 2003. This newly discovered virus is now known to have crossed the species barrier through close contact between humans and infected animals. The natural reservoir of disease has not been proved, but a number of species, including the masked palm civet, have shown infection with a related coronavirus. The virus rapidly adapted to the new host and not only became readily transmissible between humans but also more pathogenic. Contaminated sewage from a housing estate was responsible for the first outbreak of SARS in Hong Kong in 2003, before being spread worldwide by travelers and resulting in sporadic outbreaks. The long incubation period complicated containment of the disease. Control of the spread was finally accomplished in 2005 by using traditional public health measures including finding and isolating case-patients, quarantining contacts, and using enhanced infection control.

The virus is moderately infective, with an attack rate that ranges from 2.4-31 cases per 1,000 exposure hours and is transmitted by aerosolization. Globally, 8422 patients were infected and 916 died, for a case-fatality rate of approximately 15%, but this is higher in elderly persons (can exceed 50% in those >60 y) and in those with comorbid diseases.8 The disease is much milder in patients younger than 12 years (mortality rate was 0% for these patients in the Hong Kong outbreak). Mortality was much higher in patients older than 65 years and can exceed 50% for those 60 years and older.

Avian influenza H5N1 is more fulminant than other recent strains of influenza A or SARS. While it shares similar pathology to SARS, it has a 5-fold mortality compared with SARS, and children do not appear to have milder illness. Both SARS and H5N1 viruses appear to have persistence in postmortem lung tissue, which has implications for infection of contacts.9 Persistence of virus in postmortem tissue of patients with both SARS and avian influenza also indicates a failure of the drugs used to treat the disease (including ribavirin in the case of SARS) and the occasional resistance of H5N1 to oseltamivir.

RSV

RSV is important both because of the high attack rate in infants, children, and elderly adults, as well as the morbidity and mortality in these groups. Although RSV does not undergo major periodic antigenic changes as does the influenza virus, immunity is incomplete. Reinfection in children and the young is mild, but rates of severe disease and pneumonia increase with increasing age.

Adenovirus

Adenovirus serotype 14 merits special attention because of the severity of disease including high mortality and morbidity rates.10 Adenoviruses were first described in the 1950s with 52 serotypes identified so far.11 Adenoviruses are associated with a wide spectrum of clinical illnesses depending on the serotype of the infecting agent. These include asymptomatic illness, conjunctivitis, febrile upper respiratory disease, pneumonia, gastrointestinal illness, hemorrhagic cystitis, rash, and neurologic disease.

Fatalities and severe cases of pneumonia occur but had been rare until Ad 14 reemerged in the United States in 2005. Adenovirus 14 was first identified in the 1950s but was rare until identified in 2005. The new strain of Ad 14 has some genetic differences from the strain found in the 1950s. In May 2006, a fatal case of Ad 14 illness occurred in a previously healthy 12-day-old infant. Between March and June 2007, 140 cases were identified in Oregon, Washington, and Texas. Severity of disease was unusually high, with 53 patients hospitalized, including 24 requiring admission to intensive care units, and 9 deaths.10 Adenovirus 14 has also been found in healthy military recruits.12

Spread of Ad is by respiratory secretions, feces, and fomites. Neonates may acquire Ad infection from exposure to cervical secretions at birth. One neonate died of Ad pneumonia whose mother had documented cervical cells containing the Ad virus. Contaminated environmental surfaces can harbor virus capable of causing infection for weeks. The virus is resistant to lipid disinfectants but is inactivated by heat, formaldehyde, and bleach. Although adenovirus outbreaks are common among military recruits and most children show evidence of infection with adenovirus by the age of 10, the majority of illnesses had been mild and self-limiting with only supportive care until Ad 14 reappeared.

Adenoviruses are extremely contagious. Studies of new military recruits have shown Ad seroconversion rates of 34-97% over a 6-week period, and recently Ad 14 has been identified in this population12 and the majority of children have serologic evidence of prior Ad infection by the age of 10.

Some viruses are extremely fastidious, whereas others have the capability of surviving on environmental surfaces for as long as 7 hours, on gloves for 2 hours, and on hands for 30 minutes. Hantavirus transmission is thought to occur primarily through inhalation of infected excreta from diseased rodents, although the virus is also present in rodent saliva; therefore, transmission can occur during bites.

In general, patients with the greatest risk for severe disease from viral pneumonia secondary to any viral pathogen are elderly patients, patients who are immunocompromised, and those with underlying chronic illnesses. Pregnant patients are also at increased risk for morbidity and mortality. Hypoxemia and ARDS can occur in patients who are severely ill. Some patients have residual disability from interstitial fibrosis because of viral pneumonia. Infants hospitalized with lower lung infection due to RSV are much more likely to later develop asthma. Adenovirus, influenza A and B, parainfluenza, and RSV account for 70% of nosocomial pneumonias. These infections are common in patients who are institutionalized.

Pathophysiology and pathogenesis

A full understanding of the pathophysiology and pathogenesis of viral diseases does not presently exist.

The mechanism of damage to tissues depends on the virus involved. In some cases, the immune response may contribute to disease manifestation, in addition to controlling the infection and permitting a return to normal health. Immune responses can be categorized according to patterns of cytokine production. Type 1 cytokines promote cell-mediated immunity, while type 2 cytokines mediate allergic responses. Children infected with RSV who develop acute bronchiolitis, rather than mild upper respiratory infection (URI) symptoms, have impaired type 1 immunity or augmented type 2 immunity.13 In addition to humoral 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.

Respiratory viruses damage the respiratory tract and stimulate the host to release multiple humoral factors, including histamine, leukotriene C4, and virus-specific immunoglobulin E in RSV infection and bradykinin, interleukin 1, interleukin 6, and interleukin 8 in rhinovirus infections. RSV infections can also alter bacterial colonization patterns, increase bacterial adherence to respiratory epithelium, reduce mucociliary clearance, and alter bacterial phagocytosis by host cells.

Infection by influenza virus leads to cell death, especially in the upper airway. When direct viral infection of lung parenchyma occurs, hemorrhage is seen along with a relative lack of inflammatory cells. Mucociliary clearance is impaired, and bacterial adherence to respiratory epithelium occurs. Infection with the virus impairs T cells and neutrophil and macrophage function, which leads to impairment of host defenses and may foster bacterial infection of normally sterile areas, including the lower respiratory tract. This impairment of host defenses may explain why as many as 53% of outpatients with bacterial pneumonia have a concurrent viral infection.

SARS mainly attacks the pulmonary system, although a few reports have been related to other organ systems. The virus targets pneumocytes causing extensive destruction. In addition, an inflammatory and immune reaction results in diffuse alveolar damage (DAD). Bronchiolitis obliterans organizing pneumonia was described by some authors.9

Avian influenza causes a similar picture but appears more fulminant and rapid in progression. In SARS, the average duration from symptom onset to death was 19.5 days, while 6 patients died during the fifth week of illness. Pathology found in lung tissue depended on when the patient died, with lung congestion and pleural effusion being more prominent in those dying later.9

As with SARS, the pathology seen in the lungs of patients with avian influenza A/H5N1 depended on the time of death. Avian influenza resulted in extensive consolidation of the lungs with varying degrees of hemorrhage. Some patients showed bloody effusions and diffuse alveolar damage. It should be emphasized that the type of pulmonary pathology seen in both SARS and avian influenza can be seen in severe pneumonias secondary to other etiologic agents.14

Elderly persons are at increased risk of infection and complications in viral pneumonia because of comorbidities. Waning cellular, humoral, and innate immune functioning may impair viral clearance, which allows spread of the virus to the lower respiratory tract resulting in increased inflammation. Elderly persons also have decreased respiratory muscle strength and protection of the respiratory tract by mucus levels.2

Adenoviruses are associated with a wide spectrum of clinical illnesses depending on the serotype of the infecting agent. These include asymptomatic illness, conjunctivitis, febrile upper respiratory disease, pneumonia, gastrointestinal illness, hemorrhagic cystitis, rash, and neurologic disease. Adenovirus accounts for 10% of pneumonias in children. Fatalities and severe cases of pneumonia occur but are rare other than in disease due to Ad14. Some serotypes, especially 2, 3, 7, and 21 have been the cause of serious chronic morbidity after acute respiratory illness including irreversible atelectasis, bronchiectasis, bronchiolitis obliterans, and unilateral hyperlucent lung.11 An estimated 14-60% of these children will suffer some degree of permanent lung damage. Many of these patients presented with pharyngitis, tonsillitis, and bronchitis. In contrast, many of the patients with Ad 14 present with acute severe respiratory disease, which requires intensive care, mechanical ventilation, and prolonged hospitalization. Serious sequelae occurred in those who survived. Unlike other adenoviruses, Ad 14 has a high fatality and morbidity rate in healthy patients.

Little is know regarding mechanisms of pathogenicity of adenoviruses in general. Studies of Ad infection in children have identified increased production cytokines, particularly tumor necrosis factor-alpha (TNF-a), interleukin 6 (IL-6), and interleukin 8 (IL-8). Age, health of the patient, and other unknown host factors are believed to play key roles.

For more information, see Medscape's Pneumonia Resource Center and Influenza Resource Center.


Frequency

United States

Influenza is usually seen in epidemics and pandemics in late winter and early spring. Influenza viruses are the most common causes of viral pneumonia in civilian adults and are responsible for high rates of pneumonia among elderly persons who are at particular risk for severe and fatal disease.

RSV is the most common etiology of viral pneumonia in infants and children and appears to be associated with the later development of asthma.15 However, RSV has become an increasingly important pathogen in the elderly population and is now the second most commonly identified cause of pneumonia in elderly persons, causing 2-9% of the annual 687,000 hospitalizations and 74,000 deaths from pneumonia in this population.2 Some studies have suggested that RSV-related disease is as frequent as influenza in elderly persons. Approximately 10% of nursing home patients develop RSV infection annually, while 10% of these patients will develop pneumonia. RSV infection is seasonal, with rates that increase in the fall, peak in winter, and return to baseline in the spring. Peak attack rates for RSV occur in the winter in infants younger than 6 months.

Parainfluenza infection most often occurs in the late fall or winter and is the second most common viral illness, after RSV, in infants.

Adenovirus accounts for 10% of pneumonias in children. Disease from adenovirus can occur at any time of the year. Various adenovirus serotypes are responsible for essentially continuous epidemics of acute respiratory disease at military recruit training facilities in the United States and worldwide. During the prevaccination era, up to 20% of recruits had to be removed from duty due to illness.16 Unfortunately, the vaccine against adenovirus is no longer available for administration to military personnel.

International

SARS and avian influenza have become major threats to health. In the case of avian influenza, a huge economic burden has been imposed in Asia because of the need to cull infected poultry. Many epidemiologists are predicting a pandemic secondary to avian influenza, and intensive work is being done to create vaccines against both SARS and avian influenza.

Adenovirus occurs worldwide. Adenovirus 14 has been identified in Taiwan and Europe.

Mortality/Morbidity

The burden of viral pneumonia, of any etiology, can be huge.

The US census for 2000-2001 listed pneumonia/influenza as the seventh leading cause of death (down from sixth) despite a 7.2% decrease in the mortality rate for these diseases during this period. Severe influenza seasons can result in more than 40,000 excess deaths and more than 200,000 hospitalizations. Morbidity, especially in elderly persons, is also high. Up to 10-12% of patients older than 65 years required a higher level of assistance for activities of daily living after hospitalization for acute respiratory illnesses. In one nursing home outbreak, residents with acute influenza illness showed significant functional decline.18

Patients aged 65 years or older are at particular risk for death from viral pneumonia as well as from influenza not complicated by pneumonia. Deaths in these patients account for 89% of all pneumonia and/or influenza deaths. The question of the effectiveness of widespread vaccination in elderly persons is being questioned. A recent meta-analysis of the efficacy, effectiveness, and safety of the influenza vaccine in patients older than 65 years found that vaccination is of benefit to residents of long-term care facilities but in the community is of modest value.19 However, the Centers for Disease Control and Prevention (CDC) still recommend immunization of all elderly patients.20

The SARS epidemic showed a high morbidity and mortality rate. The mortality rate worldwide was approximately 10.5-15%. From 5 cohorts of patients, the ICU admission rate ranged from 20-38%. Mechanical ventilatory support was required in 59-100% of the patients in the ICU. The mortality rate of patients with SARS who were admitted to the ICU ranged from 5-67%. Mortality rates in patients older than 60 years approached 50%. Health care workers were at high risk for contracting the disease and accounted for one fifth of all cases. One year after discharge, those who survived continued to have abnormal chest radiographic findings (27.8%) and pulmonary function (23.7%).21

Sex

Age

Elderly persons have a higher risk for severe disease, but viral pneumonia can affect people of any age. Altered mental status and fever may be the only signs of influenza pneumonia in elderly, cognitively impaired patients. Cough, fever, and acute onset had only a 30% positive predictive value in elderly persons compared with a 78% positive predictive value in young adults. Elderly persons are at particular risk of death due to SARS.

Clinical

History

Most of the viruses that cause viral pneumonia present with an influenzalike syndrome consisting of fever, malaise, headache, cough, and myalgias. This presentation makes determination of the etiology, on a purely clinical basis, difficult. Ascertaining immunization status, travel history, and possible exposure is important. In very elderly persons, the only complaint may be fever and change in mental status. Most patients have cough, but in elderly persons, this may be only scant.

Rapid antigen detection kits can provide results within hours, making them useful in the ED. The sensitivity and specificity of these kits varies between 80% and 95%.

Findings with illnesses caused by influenza virus, RSV, parainfluenza, paramyxovirus measles virus, CMV, varicella-zoster virus, herpes simplex virus, SARS, avian influenza, and Hantavirus are as follows:

Physical

Some patients have few, if any, physical findings other than mild fever, whereas other patients may have respiratory and/or multiorgan failure. Other findings include the following:

Causes

Causes of viral pneumonia include influenza virus, RSV, parainfluenza virus, adenovirus, paramyxovirus, CMV, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, Hantavirus, and coronavirus SARS-CoV.

Source : http://emedicine.medscape.com/article/808013-overview
posted by hermandarmawan93 at 10:25

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