Respiratory syncytial virus infection: Diagnostic investigation, management and preventive strategies

In the current era, Respiratory Syncytial Virus (RSV) prevails as the dominant viralpathogen causing bronchiolitis in infants <2 years of age seen either in the emergency room or hospitalized with lower respiratory tract infections (LRI). The burden of illness with RSV infection is substantial, amounting to approximately 33 million cases worldwide in 2005, with accompanying morbidity and significant mortality especially in infants with underlying medical disorders and those living in developing countries. Of equal importance are high complication rates following RSV-related hospitalization inclusive of the consumption of considerable healthcare resources both within institutions and subsequently in the community. In the early phase of illness, RSV presents as an upper respiratory tract infection which is indistinguishable from the common cold. The progression to bronchiolitis and pneumonia occurs abruptly with marked respiratory distress with or without cyanosis. Pathologically, severe inflammatory changes in the lungs with mucus plugging, edema and epithelial sloughing of the airways results in clinical deterioration which merits hospitalization and intensive care in critically ill infants. Diagnosis is established by nasopharyngeal swabs or aspirates using a combination of techniques including enzyme immunoassay, direct fluorescent antibody staining, cell culture, and nucleic acid amplification tests (NAT). Nucleic acid amplification technology, particularly multiplex PCR coupled with fluidic or fixed microarrays, provides a rapid, accurate and comprehensive approach for the detection of multiple respiratory viruses that cause bronchiolitis including RSV, in a single test. Several commercial NATs are now available. More recently, the addition of allelic discrimination and detection of single nucleotide polymorphisms associated with antiviral resistance to multiplex assays coupled with new viral load tests will facilitate optimal treatment of patients during epidemics and nosocomial spread in hospitals. Numerous, well-conducted clinical trials have systematically failed to identify a sole therapeutic intervention for the treatment of RSV infection. Evaluated strategies include the use of ribavarin, steroids, bronchodilators, epinephrine, leukotrienes, DNase, antibiotics, Vitamin A and chest physiotherapy. Inhaled hypertonic saline appears safe and promising but further evidence of efficacy either alone or as part of combination therapy is awaited. Treatment of patients with respiratory failure is case dependent due to the heterogeneity of disease presentation and dynamic physiology which clouds clinicalendpoints derived from small randomized controlled studies. Guidelines on the timing and optimal mode of positive pressure and mechanical ventilation do not exist. As a result, management of infants requiring respiratory support and critical care tends to represent a fusion of clinical experience, expert opinion, extrapolation of evidence fromother respiratory illnesses and a logical approach to trial and error. Studies are in progress to determine if the use of monoclonal antibodies administered in the acute phase of RSV infection, consistently reduces viral load and perhaps severity of illness. Fusion protein inhibitors and drugs that inhibit viral replication and small interfering RNAs that target mRNA in a sequence-specific manner are under investigation. Primary prevention should focus on thorough hand washing, avoidance of potential risk factors such as smoking, crowded environments, individuals with respiratory illness and strongly encouraging breast feeding. While awaiting the genesis of an effective pediatric vaccine, genetically engineered, humanized monoclonal antibodies comprise the mainstay of RSV prevention. The efficacy and safety of palivizumab has been proventhrough two large scale multicenter, randomized controlled trials in premature infants ≤35 weeks gestational age, those with bronchopulmonary dysplasia (BPD) and hemodynamically significant congenital heart disease (CHD). The active use of palivizumab internationally has resulted in reduction in RSV related hospitalizations and complication rates in premature infants and those with BPD and CHD. Concomitantly, prophylaxis in infants with underlying medical disorders is steadily increasing and will further impact the burden of disease. More recently, motavizumab which is 18 times more potent than palivizumab in neutralizing RSV in tissue culture and has a 70-fold greater binding affinity has been demonstrated to be non-inferior to palivizumab in reducing the rate of RSV hospitalization with a 50% relative reduction in RSV-specific outpatient medicallyattended LRI. Equal efficacy has also been demonstrated through a RCT in infants with significant cardiac disease. What's in the pipeline? In adults an RSV-A vaccine generated adequate neutralizing antibodies to protect against seasonal RSV-A or B illness but further efficacy studies are required. Phase 1 trials to determine the safety, tolerability, immunogenicity and viral shedding of a pediatric, intranasally administered RSV vaccine are evolving. © 2012 Nova Science Publishers, Inc.