Overview of Viral Respiratory Infections Viral infections commonly affect the upper or lower respiratory tract. Although these infections can be classified by the causative virus (eg, influenza), they are generally classified clinically according to syndrome (eg, the common cold, bronchiolitis, croup). Although specific pathogens commonly cause characteristic clinical manifestations (eg, rhinovirus typically causes the common cold, respiratory syncytial virus [RSV] typically causes bronchiolitis), each can cause many of the viral respiratory syndromes.

Syndrome Common Causes Less Common Causes Bronchiolitis RSV Influenza viruses Parainfluenza viruses Adenoviruses Rhinoviruses Common cold Coronaviruses Enteroviruses Human metapneumoviruses Croup Influenza-like illness Pneumonia RSV = respiratory syncytial virus.

Bronchiolitis Bronchiolitis is an acute viral infection of the lower respiratory tract affecting infants < 24 mo and is characterized by respiratory distress, wheezing, and crackles. Diagnosis is suspected by history, including presentation during a known epidemic; the primary cause, respiratory syncytial virus, can be identified with a rapid assay. Bronchiolitis often occurs in epidemics and mostly in children < 24 mo, with a peak incidence between 2 mo and 6 mo of age. Etiology Most cases of bronchiolitis are caused by Respiratory syncytial virus (RSV) Rhinovirus Parainfluenza virus type 3 Less frequent causes are influenza viruses A and B, parainfluenza viruses types 1 and 2, metapneumovirus, adenoviruses, and Mycoplasma pneumoniae.

Pathophysiology The virus spreads from the upper respiratory tract to the medium and small bronchi and bronchioles, causing epithelial necrosis and initiating an inflammatory response. The developing edema and exudate result in obstruction, which leads to alveolar air trapping. Diagnosis Clinical presentation Pulse oximetry Chest x-ray for more severe cases RSV antigen test on nasal washings or nasal aspirates for seriously ill children Prognosis Prognosis is excellent. Most children recover in 3 to 5 days without sequelae, although wheezing and cough may continue for 2 to 4 wk. Mortality is < 0.1% when medical care is adequate. Treatment Supportive therapy

Croup (Laryngotracheobronchitis) Croup is acute inflammation of the upper and lower respiratory tracts. Croup affects mainly children aged 6 mo to 3 yr. Etiology The most common pathogens are Parainfluenza viruses, especially type 1 Less common causes are respiratory syncytial virus (RSV) and adenovirus followed by influenza viruses A and B, enterovirus, rhinovirus, measles virus, and Mycoplasma pneumoniae. Croup caused by influenza may be particularly severe and may occur in a broader age range of children. Seasonal outbreaks are common. Cases caused by parainfluenza viruses tend to occur in the fall; those caused by RSV and influenza viruses tend to occur in the winter and spring. Spread is usually through the air or by contact with infected secretions. Pathophysiology The infection causes inflammation of the larynx, trachea, bronchi, bronchioles, and lung parenchyma. Obstruction caused by swelling and inflammatory exudates develops and becomes pronounced in the subglottic region. The illness usually lasts 3 to 4 days and resolves spontaneously. The vast majority of children with croup recover completely.

Adenovirus Infections Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Pneumonia is the most common fatal hospital-acquired infection and the most common overall cause of death in developing countries. Adenovirus Infections Infection with one of the many adenoviruses may be asymptomatic or result in specific syndromes, including mild respiratory infections, keratoconjunctivitis, gastroenteritis, cystitis, and primary pneumonia. Diagnosis is clinical. Treatment is supportive. Adenoviruses are commonly acquired by contact with secretions (including those on fingers of infected people) from an infected person or by contact with a contaminated object (eg, towel, instrument). Infection may be airborne or waterborne (eg, acquired while swimming). Asymptomatic respiratory or GI viral shedding may continue for months, or even years.

Symptoms and Signs Most adenovirus infections are asymptomatic; when infections are symptomatic, a broad spectrum of clinical manifestations is possible. The most common syndrome, especially in children, involves fever that tends to be > 39° C and to last > 5 days. Sore throat, cough, rhinorrhea, or other respiratory symptoms may occur. A separate syndrome involves conjunctivitis, pharyngitis, and fever (pharyngoconjunctival fever). Rare adenoviral syndromes in infants include severe bronchiolitis and pneumonia. Most patients recover fully. Even severe primary adenoviral pneumonia is not fatal except for rare fulminant cases, predominantly in infants, military recruits, and immunocompromised patients.

Diagnosis Clinical evaluation Laboratory diagnosis of adenovirus infection rarely affects management. During the acute illness, virus can be isolated from respiratory and ocular secretions and frequently from stool and urine. A 4-fold rise in the serum antibody titer indicates recent adenoviral infection. Treatment Treatment is symptomatic and supportive.  Prevention Vaccines containing live adenovirus types 4 and 7, given orally in an enteric-coated capsule, can reduce lower respiratory disease. It may be given to patients aged 17 through 50 yr and should not be given to women who are pregnant or breastfeeding.

Influenza (Flu) Influenza is a viral respiratory infection causing fever, coryza, cough, headache, and malaise. Mortality is possible during seasonal epidemics, particularly among high-risk patients (eg, those who are institutionalized, at the extremes of age, have cardiopulmonary insufficiency, or are in late pregnancy). Influenza viruses are classified as type A, B, or C by their nucleoproteins and matrix proteins. Influenza C virus infection does not cause typical influenza illness and is not discussed here. Influenza antigens Hemagglutinin (H) is a glycoprotein on the influenza viral surface that allows the virus to bind to cellular sialic acid and fuse with the host cell membrane. Neuraminidase (NA), another surface glycoprotein, enzymatically removes sialic acid, promoting viral release from the infected host cell. There are 18 H types and 11 NA types, giving 198 possible combinations, but only a few are human pathogens. Antigenic drift refers to relatively minor, progressive mutations in preexisting combinations of H and NA antigens, resulting in the frequent emergence of new viral strains. These new strains may cause seasonal epidemics because protection by antibody generated to the previous strain is decreased. Antigenic shift refers to the relatively rare development of new combinations of H and/or NA antigens, which result from reassortment of subunits of the viral genome. Pandemics can result from antigenic shift because antibodies against other strains (resulting from vaccination or native infection) provide little or no protection against the new strain.

Epidemiology Influenza causes widespread sporadic illness yearly during fall and winter in temperate climates (seasonal epidemics). Seasonal epidemics are caused by both influenza A and B viruses. Influenza B viruses may cause milder disease but often cause epidemics with moderate or severe disease, usually in 3- to 5-yr cycles. Influenza viruses can be spread by airborne droplets, person-to-person contact, or contact with contaminated items. Airborne spread appears to be the most important mechanism. At-risk groups Children < 4 yr Adults > 65 yr People with chronic medical disorders (eg, cardiopulmonary disease, diabetes mellitus, renal or hepatic insufficiency, hemoglobinopathies, immuodeficiency) Women in the 2nd or 3rd trimester of pregnancy Patients ≤ 18 yr taking aspirin (because Reye syndrome is a risk)

The incubation period ranges from 1 to 4 days with an average of about 48 h. After 2 to 3 days, acute symptoms rapidly subside, although fever may last up to 5 days. Cough, weakness, sweating, and fatigue may persist for several days or occasionally for weeks. Diagnosis Clinical evaluation Sometimes rapid diagnostic testing Prognosis Most patients recover fully, although full recovery often takes 1 to 2 wk. However, influenza and influenza-related pneumonia are important causes of increased morbidity or mortality in high-risk patients.

Drugs for influenza Antiviral drugs given within 1 to 2 days of symptom onset decrease the duration of fever, severity of symptoms, and time to return to normal activity. Treatment with antiviral drugs is recommended for high-risk patients who develop influenza-like symptoms. Drugs for influenza include the following: Oseltamivir and zanamivir (neuraminidase inhibitors) Amantadine and rimantadine (adamantanes) Neuraminidase inhibitors interfere with release of influenza virus from infected cells and thus halt spread of infection. Adamantanes block the M2 ion channel and thus interfere with viral uncoating inside the cell. They are effective only against influenza A viruses (influenza B viruses lack the M2 protein).

Prevention Influenza infections can largely be prevented by Annual vaccination Sometimes chemoprophylaxis (ie, with antiviral drugs) Current commercially available vaccines protect only against seasonal influenza. Vaccines vaccines are modified annually to include the most prevalent strains (usually 2 strains of influenza A and 1 or 2 strains of influenza B). When the vaccine contains the same HA and NA as the strains in the community, vaccination decreases infections by 70 to 90% in healthy adults. In the institutionalized elderly, vaccines are less effective for prevention but decrease the rate of pneumonia and death by 60 to 80%. Vaccine-induced immunity is decreased by antigenic drift and is absent if there is antigenic shift. There are 2 basic types of vaccine: Multivalent inactivated influenza vaccine (MIV) given by IM. Live-attenuated influenza vaccine (LAIV) given intranasally.

Avian Influenza (Bird Flu) Avian influenza is caused by strains of influenza A that normally infect only wild birds and domestic poultry (and sometimes pigs). Infections due to these strains have recently been detected in humans. . Infections with these strains are asymptomatic in wild birds but may cause highly lethal illness in domestic poultry. It is likely that avian influenza viruses of any antigenic specificity can cause influenza in humans whenever the virus acquires mutations enabling it to attach to human-specific receptor sites in the respiratory tract. Because all influenza viruses are capable of rapid genetic change, there is a possibility that avian strains could acquire the ability to spread more easily from person to person via direct mutation or via reassortment of genome subunits with human strains during replication in a human, animal or, avian host. Human infection with avian influenza H5N1 strains can cause severe respiratory symptoms. Mortality was 33% in the 1997 outbreak and has been > 60% in subsequent infections. Diagnosis Reverse transcriptase–PCR (RT-PCR)

Pandemic 2009 H1N1 Influenza (Swine Flu) The H1N1 swine flu virus is a combination of swine, avian, and human influenza viruses that spreads easily from person to person. The infection is not acquired through ingestion of pork and is acquired very rarely by contact with infected pigs. In June 2009, the World Health Organization declared H1N1 swine flu a pandemic; it spread to > 70 countries and to all 50 US states. Symptoms are usually mild, but they can become severe, leading to pneumonia or respiratory failure. Diagnosis A PCR test can detect the A(H1N1)pdm09 virus in respiratory tract samples (eg, nasopharyngeal swabs, nasal washings, tracheal aspirates). Treatment Sometimes a neuraminidase inhibitor Treatment focuses mainly on symptom relief . Prevention The current seasonal influenza vaccines are effective against the A(H1N1)pdm09 virus. Commonsense steps (eg, staying home if influenza-like symptoms develop; thorough, frequent handwashing with soap and water or an alcohol-based hand sanitizer) are recommended to reduce the spread of infection.

Parainfluenza Virus Infections Parainfluenza viruses include several closely related viruses that cause many respiratory illnesses varying from the common cold to an influenza-like syndrome or pneumonia; croup is the most common severe manifestation. The parainfluenza viruses are paramyxoviruses types 1, 2, 3, and 4. They share antigenic cross-reactivity but tend to cause diseases of different severity. The most common illness in children is an upper respiratory illness with no or low-grade fever. Parainfluenza type 1 probably causes croup (laryngotracheobronchitis), primarily in infants aged 6 to 36 mo. Respiratory failure due to upper airway obstruction is a rare but potentially fatal complication. Parainfluenza virus type 3 may cause pneumonia and bronchiolitis in young infants. These illnesses are generally indistinguishable from disease caused by respiratory syncytial virus but are often less severe.

Coronaviruses and Acute Respiratory Syndromes (MERS and SARS) Coronaviruses are enveloped RNA viruses. Two coronaviruses, MERS-CoV and SARS-CoV, cause much more severe respiratory infections in humans than other coronaviruses. MIDDLE EAST RESPIRATORY SYNDROME (MERS) Person-to-person transmission has been established. The reservoir of MERS-CoV is unknown; however, many coronavirus species are present in bats, . Anti-MERS-CoV antibodies have been detected in a few camels, which are the only other currently suspected hosts. The incubation period is about 5 days. More than half of cases have been fatal. Median patient age is 56 yr, and the male:female ratio is about 1.6:1. Infection tends to be more severe in elderly patients and in patients with a preexisting disorder such as diabetes, a chronic heart disorder, or a chronic renal disorder. Fever, chills, myalgia, and cough are common. Diagnosis Real-time reverse-transcriptase PCR (RT-PCR) testing of lower respiratory secretions Treatment Supportive