Infectious Disease and Microbiology – Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is a highly contagious viral infection that causes upper and lower respiratory tract disease in children and adults. It is particularly important in infants, children with congenital heart or chronic lung disease, immunocompromised individuals, and older adults. Acute bronchiolitis is the major clinical manifestation in young children.

RSV is one of the most important causes of lower respiratory tract infection in childhood. In 2005, an estimated 33.8 million episodes of RSV-associated acute lower respiratory tract infection occurred worldwide among children younger than 5 years, with an estimated 66,000–199,000 associated deaths. Severe RSV disease occurs most frequently between 2 and 8 months of age. By 24 months, most children have experienced at least one RSV infection. RSV also causes substantial disease in older adults, with annual attack rates historically estimated at approximately 5–10%.

Important risk factors for severe RSV infection include age younger than 6 months, prematurity, male sex, crowding, lower socioeconomic conditions, exposure to passive cigarette smoke, day-care attendance, older siblings attending day care, and birth during the early part of RSV season. Children with congenital heart disease, chronic lung disease such as bronchopulmonary dysplasia or cystic fibrosis, and individuals who are immunocompromised because of chemotherapy or transplantation are also at increased risk.

Prevention focuses on reducing viral transmission and protecting individuals at high risk of severe disease. Frequent handwashing, avoiding the sharing of contaminated objects, and appropriate infection-control precautions can reduce transmission. Glove and gown precautions are particularly important in healthcare environments. Historically, passive immunization with RSV-specific immunoglobulin and the monoclonal antibody palivizumab has been used for selected high-risk infants. Motavizumab was investigated as a more potent monoclonal antibody against RSV.

RSV spreads from the upper respiratory tract into the lower respiratory tract. Viral infection promotes cell-to-cell fusion, producing characteristic multinucleated structures known as syncytia. Infection and inflammation of the small airways contribute to airway obstruction, mucus production, wheezing, and the characteristic manifestations of bronchiolitis.

Severe RSV bronchiolitis during infancy has been associated with an increased prevalence of recurrent wheezing and asthma later in childhood. Some studies have suggested that RSV prophylaxis may reduce recurrent wheezing in certain nonatopic children, although the relationship between RSV infection, atopy, and subsequent asthma is complex.

The incubation period of RSV is approximately 2–8 days. Transmission occurs through contact with infected respiratory secretions, contaminated hands or surfaces, and respiratory droplets. Infection commonly begins with upper respiratory symptoms and may progress rapidly to cough, coryza, and wheezing. Fever is usually low-grade, although high fever can occur in children.

As the disease progresses, young children may develop a deeper cough, episodes of coughing, wheezing, and manifestations of bronchiolitis. Mild croup may occur, and otitis media is a frequent associated condition. Older adults may develop more significant lower respiratory tract disease, including bronchopneumonia.

Physical examination of infants with RSV lower respiratory tract infection may demonstrate tachypnea, diffuse rales associated with small-airway disease, wheezing, and, in severe cases, cyanosis. Otitis media may also be present. Careful assessment of hydration is particularly important in infants and should include evaluation of skin turgor, capillary refill, and the condition of the mucous membranes.

Laboratory assessment in patients with significant illness may include measurement of oxygen saturation, arterial blood gases, serum electrolytes, and a complete blood count. RSV can be identified from respiratory secretions using rapid diagnostic tests. Other diagnostic techniques include immunofluorescence assays, enzyme-linked immunosorbent assays, and viral culture of nasal washings.

Chest radiographs may demonstrate hyperinflation, focal atelectasis, and pulmonary infiltrates. Expiratory CT imaging may show evidence of small-airway disease, particularly air trapping. Histopathologic examination of lung tissue can demonstrate mononuclear cell and neutrophil infiltration around bronchioles, together with areas of atelectasis and pulmonary infiltrates.

The differential diagnosis includes asthma, acute or chronic bronchitis, bacterial or viral pneumonia, influenza, parainfluenza infection, croup, human metapneumovirus infection, and neonatal sepsis.

Treatment is primarily supportive. Oxygen should be administered when clinically indicated, and adequate hydration should be maintained with oral or intravenous fluids depending on the patient’s condition. Respiratory support, including mechanical ventilation or intubation, may be necessary in severe disease.

Nebulized ribavirin has historically been approved for severe RSV infection. A regimen described is 6 g of lyophilized ribavirin dissolved in 300 mL of distilled water and administered through a small-particle aerosol generator for 12–20 hours per day for 3–7 days. However, evidence supporting substantial clinical benefit has been limited, and concerns include cost and potential occupational exposure of healthcare workers. Its use has therefore generally been reserved for selected severe cases, particularly among profoundly immunocompromised patients.

Various additional approaches have been investigated in high-risk populations. Intravenous palivizumab, alone or in combination with ribavirin, has been studied in severe RSV infection. Combination regimens involving inhaled ribavirin, corticosteroids, intravenous immunoglobulin, and sometimes palivizumab have also been evaluated in transplant recipients. RNA interference therapies have additionally been investigated in lung transplant patients.

Hospitalized patients require careful supportive management. Oxygenation and hydration should be monitored closely, and patients with progressive respiratory failure may require assisted ventilation. Young infants, immunocompromised patients, individuals with significant cardiopulmonary disease, and older adults are at increased risk of severe outcomes.

Most otherwise healthy children hospitalized with RSV infection improve sufficiently for discharge within several days. Follow-up is generally unnecessary after uncomplicated recovery, although patients who subsequently develop persistent or recurrent bronchospasm may require additional evaluation.

The prognosis is generally favorable in healthy children, but RSV can cause substantial morbidity and mortality in young infants, older adults, and individuals with underlying cardiopulmonary disease or immunocompromising conditions. A small but important proportion of infants with RSV infection require intermediate or intensive care.

Potential complications include bacterial pneumonia, otitis media, respiratory failure, and recurrent wheezing. Neurologic complications such as seizures and encephalopathy have also been reported. Severe childhood RSV infection has been associated with subsequent asthma or recurrent wheezing, although the precise causal relationship remains uncertain.