Case 1

1. What type of isolation should the patient be put in? 

Transmission is via contact with respiratory droplets. Because RSV can cause nosocomial infections, patients should be put in contact isolation. If patients are not isolated and infection control practices (strict hand-washing, use of gloves and gowns, etc.) are not used, cross-infections can occur at a rate of 20 to 50%. Several patients with RSV can be "cohorted" (put in the same room), and their health care providers can be similarly cohorted. Nosocomial RSV infections are a hazard particularly for other hospitalized patients with congenital heart disease, lung disease, or immunodeficiency states who are at risk for life-threatening RSV infections.

Community outbreaks of RSV infection occur annually and can commence at any time from late fall to early spring. The usual outbreak lasts 8 to 12 weeks and can involve nearly one half of all families with children. In the family setting, it appears that older siblings often introduce the virus into the home, and secondary infection rates can be almost 50%. The usual duration of virus shedding is 5 to 7 days; young infants, however, may shed virus for 9 to 20 days or longer.

2. What is known about the pathogenesis of the infection? 

The virus is spread to the upper respiratory tract by contact with infective secretions. Infections appear to be confined primarily to the respiratory epithelium, with progressive involvement of the middle and lower airways. Viremia occurs rarely.

The virus particles are also toxic to tissues. This toxicity can be demonstrated by inoculating high concentrations of inactivated virions into mice, which produces acute inflammatory changes in the absence of viral penetration or replication within cells.

The apparent enhanced severity of disease, particularly in very young infants, is not yet clearly understood, but may have an immunologic basis. Factors that have been proposed to play a role include (1) qualitative or quantitative deficits in humoral or secretory antibody responses to critical virus-specified proteins; (2) excessive damage from inflammatory cytokines or direct cell-mediated cytotoxicity; (3) formation of antigen-antibody complexes within the respiratory tract resulting in complement activation; and (4) IgE-mediated histamine release.

The usual mortality among infants hospitalized with RSV infections is 0.5 to 1%; however, this rises to 15% or greater in children receiving cancer chemotherapy, infants with congenital heart disease, and those with severe immunodeficiency. Infants with underlying chronic lung disease are also considered to be at high risk for a lethal outcome. Former premies are also high risk-tend to have bronchopulmonary displasia from prolonged ventillation.

3. Describe the rapid test used for detection of RSV. 

Rapid antigen detection tests are currently available for RSV and influenza A. RSV can be detected in nasopharyngeal washings or aspirates by either an enzyme immunoassay (EIA) or immunofluorescence. Many institutions are replacing immunofluorescence with EIA because EIA is easier to perform, is more rapid when multiple specimens must be tested, and has similar sensitivity and specificity. RSV isolation in cell culture takes 3 to 10 days. The advantage of culture is a higher degree of sensitivity than that of rapid procedures, and culture has the ability to detect a variety of viral agents. However, specimens for RSV culture must be quickly transported and cultured because this virus soon loses infectivity outside the host. Rapid viral antigen tests are valuable because of the length of time required to detect many viruses in culture. Prompt results are preferred so that the decision to use antiviral agents can be made as soon as possible.

4. A formalin fixed-killed virus vaccine was tested against RSV. Why was this vaccine discontinued?

This vaccine was discontinued because it predisposed children to more severe disease!

5. Describe the preventative therapy currently in use for selected infants. 

Palivizumab and RespiGam are currently used to prevent RSV infection in high risk infants.

Only one antiviral agent, ribavirin, is available for treatment of RSV in infants. It has been shown to decrease viral shedding and may increase the patient's oxygenation. It is delivered by aerosol to best reach the site of infection and to minimize toxicity. It is generally only given to the highest risk patients because of its extreme cost (>$1000/day).

Ribavirin is a nucleoside analogue and is thought to inhibit the viral RNA-dependent RNA polymerase.

6. Is this child likely to be reinfected? 

Yes. Immunity is short-lived and multiple reinfections are possible. However, subsequent disease is generally less severe.