Respiratory Syncytial Virus and Human Metapneumovirus

Definition

Respiratory syncytial virus (RSV), which causes yearly winter outbreaks in temperate climates, is the most important cause of bronchiolitis and pneumonia in young infants, a common cause of illness in older children and young adults, and can be severe in elderly persons, adults with underlying cardiopulmonary disease, and adults who are severely immunocompromised.

Epidemiology

In the United States epidemics begin in the south in late fall, move steadily north, and peak in February and March in colder climates. In tropical areas, RSV may occur throughout the year, with peaks during the rainy season. RSV annually causes approximately 100,000 hospitalizations and accounts for 60% of bronchiolitis and 25% of pneumonia cases in infants. Mortality is rare in the United States (<400 deaths annually), but deaths are substantially greater in developing countries. About half of infants become infected in their first winter and all by age 2. RSV is transmitted principally by direct contact with large-particle fomites of respiratory secretions rather than by small-particle aerosolization.

Between 1 and 3% of primary infections result in hospitalization, but lower socioeconomic status, crowding, underlying prematurity, congenital cardiac abnormalities, bronchopulmonary dysplasia, and immunosuppression are each associated with increased risk for serious disease. Severe disease is also associated with specific polymorphisms in the promoter regions of cytokine genes. Hospitalization is most frequent between the ages of 1 and 6 months, peaking at 2 months of age with a rate of 25.9 per 1000 children. However, the majority of hospitalized infants are normal healthy infants without identifiable risk factors. The overall burden of RSV in infants 0 to 6 months of age is 132 office visits, 55 emergency department visits, and 17 hospitalizations per 1000. Reinfection occurs frequently throughout life. Subsequent illness is less severe and hospitalization infrequent for persons ages 2 to 49 years, but severity increases with increasing age and comorbid conditions such as diabetes, heart failure, chronic obstructive pulmonary disease, and end-stage renal disease.

Though often not considered in adults, RSV infection is common and may be severe in the elderly. RSV accounts for 15 to 20% of medically attended outpatient respiratory illnesses in persons older than 45 years, and RSV-associated mortality among persons age 65 and older is about 90% as high as influenza A and greater than double that of influenza B. RSV infection is implicated in 6 to 15% of hospitalizations for acute pulmonary symptoms in the winter among community-dwelling elderly persons, numbers that are similar to those for influenza.

RSV infection has been documented in up to 10% of bone marrow transplant recipients ( Chapter 163 ), patients with acute leukemia ( Chapter 168 ), and heart/lung transplant recipients ( Chapters 46 and 87 ) during the winter months. In this setting, in-hospital outbreaks can develop quickly if patients are not adequately isolated.

Pathobiology

The virus most commonly enters through the nose or eye and then spreads from the upper to the lower respiratory tract. Pathologic findings include a lymphocytic peribronchiolar infiltration with edema, obstruction, and necrosis. Bronchiolitis with multiple areas of atelectasis and pneumonia with interstitial infiltration of mononuclear cells, as well as alveoli filled by edema and necrosis, develop in infected patients.

Clinical Manifestations

Infants experience upper respiratory symptoms of conjunctival injection, mucopurulent nasal discharge, cough, and low-grade fever after an incubation period of 2 to 8 days. Otitis media ( Chapter 394 ) is often associated with secondary bacterial infection. After several days, lower respiratory tract symptoms appear in 25 to 50% of infants, with cough, wheezing, tachypnea, and use of accessory muscles as the disease progresses. Expiratory wheezes, rhonchi, and fine rales are the most common findings on lung examination. Sudden apnea may develop in the youngest infants. Hyperinflation and diffuse interstitial pneumonitis are the most frequent radiographic findings. High-titer virus shedding lasts 7 to 10 days, although immunocompromised infants may excrete virus for a month or longer, even when asymptomatic. Coinfection with other respiratory viruses occurs in up to 30% of patients, but it usually is neither clinically discernible nor definitively associated with more severe illness.

Adults with RSV typically begin with upper respiratory symptoms, but many patients have lower respiratory symptoms, including dyspnea and wheezing. Low-titer virus shedding often persists for 10 days or longer. In elderly persons, RSV attack rates are 3 to 5% annually; wheezing is more common than with influenza ( Chapter 332 ), whereas fever is less common. Symptoms can progress to respiratory failure, especially in frail elderly persons, nursing home residents, or patients with underlying chronic obstructive pulmonary disease or heart failure. Attack rates in nosocomial nursing home outbreaks average 10 to about 90%, with crackles and wheezes evident in a third of patients and radiographically confirmed pneumonia in approximately 10%. The incidence of bacterial superinfection in hospitalized adults with RSV is about 30%, similar to that of other common respiratory viruses, including influenza.

In bone marrow transplant recipients, RSV usually presents initially with upper respiratory symptoms. In about 30% of patients, lower respiratory tract disease follows, often with severe symptoms.