Outline the treatment and management options available for the respiratory syncytial virus. Describe interprofessional team strategies for improving care coordination and communication to advance the treatment of respiratory syncytial virus and improve outcomes. Access free multiple choice questions on this topic. The mainstay of treatment for the vast majority of RSV infections is supportive, but passive preventive immunization is available for at-risk children, including premature infants and infants with a history of cardiac, pulmonary, or neuromuscular diseases.
There is a single antiviral treatment for RSV currently approved, but its use is limited by questionable efficacy, side effects, and cost, and it is recommended that it be used only for patients at risk for severe disease, on a case-by-case basis. RSV was discovered in chimpanzees in and subsequently confirmed to be a human pathogen shortly after that.
There are several animal respiratory syncytial viruses in the same genus as human RSV, which do not infect humans, and which will not be further referenced in this article. The structure of RSV is that of a bilipid-layer-envelope surrounding a ribonucleoprotein core, with several membrane proteins, one of which functions in attachment to host cells, and one of which functions in fusion to host cells.
There is only one serotype of RSV, but it is classified into two strains, "A" and "B," with differences consisting of variation in the structure of several structural membrane proteins, most especially the attachment protein. RSV is a widespread pathogen of humans, due in part to the lack of long-term immunity after infection, making reinfection frequent.
The majority of patients with RSV will have an upper respiratory illness, but a significant minority will develop lower respiratory tract illness, predominantly in the form of bronchiolitis.
Worldwide, it is estimated that RSV is responsible for approximately 33 million lower respiratory tract illnesses, three million hospitalizations, and up to , childhood deaths; the majority of deaths are in resource-limited countries.
There is seasonal variation in RSV incidence, but seasonal effects vary with worldwide geography; temperate climates have a marked winter-spring predominance, and tropical and equatorial climates may have less pronounced spikes with the more interseasonal disease.
Morbidity and mortality are significantly higher in a subset of patients, including premature infants, patients with preexisting cardiac, pulmonary, neurologic, and immunosuppressive disorders, and the elderly. RSV is spread from person to person via respiratory droplet, and the incubation period after inoculation with RSV ranges from 2 to 8 days, with a mean incubation of 4 to 6 days, depending on host factors such as the age of the patient and whether it is the patient's primary infection with RSV.
After inoculation into the nasopharyngeal or conjunctival mucosa, the virus rapidly spreads into the respiratory tract, where it targets its preferred growth medium: apical ciliated epithelial cells. There it binds to cellular receptors using the RSV-G glycoprotein, then uses the RSV-F fusion glycoprotein to fuse with host cell membranes and insert its nucleocapsid into the host cell to begin its intracellular replication.
Host inflammatory immune response is triggered, including both humoral and cytotoxic T-cell activation, and a combination of viral cytotoxicity and the host's cytotoxic response cause necrosis of respiratory epithelial cells, leading to downstream consequences of small airway obstruction and plugging by mucus, cellular debris, and DNA. More severe cases may also include alveolar obstruction. Other downstream effects include ciliary dysfunction with impaired mucus clearance, airway edema, and decreased lung compliance.
Histopathology does not play a significant role in the diagnosis of RSV and the findings in mild disease are not known, but histopathologic findings of severe disease include abundant respiratory epithelial cell death, airway edema, and immune cell infiltration, initially polymorphonuclear early in the illness, and later in the illness, lymphomononuclear.
RSV typically manifests as an upper respiratory illness, with the possibility of lower respiratory tract involvement, and historical and examination findings differ based on the location and severity of the disease. If limited to the upper respiratory tract, RSV presents with rhinorrhea, nasal congestion, cough, sneezing, and sometimes fever and myalgia. In some patients, especially those with risk factors for severe disease who are under the age of 2 years, RSV will progress to lower respiratory tract involvement with various permutations of the classic findings of bronchiolitis: rhonchorous breath sounds, tachypnea, accessory muscle use, wheezes, and prolonged expiration.
In severe cases, it may also present with findings of viral pneumonia, hypoxia, lethargy, apnea, and acute respiratory failure. The diagnosis of RSV and subsequent bronchiolitis is clinical and does not require confirmatory testing or imaging. Testing for RSV is discouraged unless the fact of its presence would alter medical decision-making. Specific testing for RSV may be useful to differentiate from other disorders and is available in two commonly used forms: rapid antigen testing and polymerase-chain-reaction-based PCR testing.
Antigen testing is quick, inexpensive, specific, and is easily performed on nasal secretions. PCR testing is increasingly more common due to the proliferation of the technology, rapid results, ease of testing, a higher sensitivity rate than antigen testing, and the ability to detect numerous other organisms when performed as part of a PCR panel. The disadvantages of PCR testing include the cost of the test and the need for specialized equipment to process the test.
Radiographic findings in RSV are identical to bronchiolitis in general, and are non-specific, and require interpretation in the context of the patient's illness. Chest x-ray findings of RSV bronchiolitis may include hyperinflation, patchy atelectasis, and peribronchial thickening; however, these may be difficult to distinguish from bacterial pneumonia.
Treatment for RSV falls into three categories: supportive care, immune prophylaxis, and antiviral medication. The majority of RSV and bronchiolitis cases require no specific medical intervention, and many attempted treatments throughout history are ineffective. There have been several attempts to meet the need for RSV therapeutics, and there are a number of promising therapeutic strategies that have been developed for the treatment of RSV infection, summarized in Table 2.
Some of these experimental therapeutic strategies have undergone clinical trials. It will be interesting to see whether GS can be used to treat RSV infection in pediatric patients, the elderly, and the immunocompromised. As shown in Table 2 , however, the vast majority of these agents are still in the preliminary stages of research either in cell culture models of infection or in protein binding studies.
From a historical perspective, nucleoside analogues that inhibit the function of the RSV polymerase are a rather obvious approach for the treatment of RSV infection. A more recently developed nucleoside analogue, marketed by Gilead Pharmaceuticals as Sovaldi, is now the basis of a cure for hepatitis C virus infection , with several more promising drugs and preparations in various stages of development.
With regard to RSV therapeutic development, a robust in vitro RSV polymerase system , , has been used to test nucleoside analogue libraries and other small-molecule inhibitors for their ability to inhibit the RSV polymerase complex. Successful clinical trials are not a guarantee of safety, however. Hazards related to nucleoside analogue-based antiviral therapeutics have been discovered after initial safety trials were completed In summary, efficacy and safety considerations of one successful hit are not sufficient to treat the spectrum of patients who are susceptible to RSV, so there is still a large unmet need for the development of more RSV antivirals.
Many different RSV preclinical therapeutic approaches are being developed Table 2. Several agents such as glycosaminoglycan binding peptides or decoy liposomes interrupt the binding of the virus to receptors on the host cell membrane. Of the more preliminary agents under investigation, the most general mechanism of inhibitor activity is inactivation of the virus particle through interaction with an agent such as gold nanoparticles Multipronged approaches are the combined inhibition of viral attachment, entry, and budding e.
There are also host-directed therapeutic strategies being developed that modulate host immune responses such as apoptosis and inflammation that favor viral clearance e. However, the progress made in RSV vaccines and therapeutics since the discovery of the virus in has been poor, particularly compared to other viruses like influenza virus, hepatitis C virus, and HIV.
There is a tremendous amount that we know about RSV replication, and several steps in the replication cycle have been identified that can be exploited as antiviral therapeutic strategies.
Our understanding of RSV replication is gradually leading to development of new therapeutics, and there will likely be new therapeutic developments trickling out as clinical trials continue. In summary, with all that we know about RSV and the prevalence, morbidity, and mortality caused by this virus, it is difficult to understand why there is such a disproportionate availability of prophylactic and therapeutic options to treat RSV disease.
The development of several rapid RSV detection tests over three generations has refined point-of-care testing. However, caution must be employed to ensure that the wealth of information on RSV infections in the community is not lost to unreported bedside testing.
Carefully designed reporting programs that gather RSV diagnostic data from a wide variety of clinical sources are therefore needed.
A promising sign of things to come is the growing number of clinical vaccine trials that are being conducted. RSV has proven particularly adept at either suppressing or evading B cell memory, and so there is the question of whether a vaccine can be developed that will elicit lasting RSV-neutralizing antibodies in the mucosae. If these hurdles can be overcome, vaccination of prepartum mothers with a robust anti-RSV vaccine would likely confer significant protection through passive immunity in infants.
Eventually, a number of vaccination options should become available for the protection of children and the elderly, who are also at significant risk from RSV infection. RSV infection surveillance through point-of-care and laboratory tests will be needed to monitor the effectiveness of new vaccines and therapeutics in the community.
As discussed in this review, there is significant evidence to suggest that vaccine escape mutations will evolve that would require established and well-run RSV surveillance programs, on par with influenza vaccine monitoring, to refine existing vaccines and therapeutics.
Cameron Griffiths, Ph. He earned his B. His honors thesis was written on the molecular biology of toxic effector proteins in the type VI secretion system of the seventh pandemic strain of cholera. He is now a Ph. Steven J. Drews , Ph. Since then, he has focused on both the clinical microbiology and research aspects of respiratory infections and has been involved in respiratory virus surveillance and preparedness planning at a national level in Canada.
Drews currently heads the province-wide influenza and acute respiratory viral diagnostics program at ProvLab Alberta. Drews has held faculty positions at both the University of Toronto and the University of Calgary. David J. Marchant earned his Ph. He completed his postdoctoral studies in cardiopulmonary virology in the Department of Pathology and Laboratory Medicine at the University of British Columbia, Canada.
His research is deciphering multitasking roles for proteins during antiviral immunity and studying the host cell factors that mediate entry of respiratory syncytial virus RSV into cells. National Center for Biotechnology Information , U.
Journal List Clin Microbiol Rev v. Clin Microbiol Rev. Published online Nov Author information Copyright and License information Disclaimer. Corresponding author. Address correspondence to Steven J. Drews, ac. Marchant, ac. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev — All Rights Reserved. This article has been cited by other articles in PMC.
SUMMARY Respiratory syncytial virus RSV infection is a significant cause of hospitalization of children in North America and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. Overall Impact: Mortality and Health Care Costs RSV causes significant pediatric and adult morbidity and mortality, which have a significant economic impact on health care systems.
Epidemiological Considerations While the overall single greatest risk factor for severe RSV infection is age 4 , several epidemiological studies have identified factors that can compound the severity of RSV infection. Comorbidities Although age is the single biggest susceptibility factor during RSV infection, there are notable factors that significantly contribute to the risk of RSV infection.
The Elderly: Susceptibility to RSV RSV is a significant cause of influenza-like illness ILI in those 65 years of age and older worldwide 63 , 64 ; reviewed in reference 5 , which has been recognized as a significant cause of morbidity and mortality in the elderly since the s 7 , 8.
Entry of RSV and Its Host Cell Receptors Obvious targets for therapeutic development are the receptors that viruses bind to trigger entry into the host cell. Open in a separate window.
FIG 1. FIG 2. Virus Transcription, Translation, and Genome Replication Elucidation of viral transcriptional processes is essential to develop viral replicon systems that can be used to screen inhibitors and develop antiviral drugs FIG 3. Correlates of Immune Protection from RSV Protection and clearance of RSV infection are likely mediated by a balance of neutralizing antibodies of the humoral immune response and cytotoxic T cells of the cell-mediated immune response Eosinophilic Infiltration of Airways during RSV Disease Histopathological analysis of autopsy samples demonstrated elevated levels of eosinophils in the airways of infants who succumbed to RSV infection 11 , which can be observed in mouse models of RSV infection Gross Pathological Signs of RSV Infection Most of the information that is available about the gross pathological signs of RSV infection is observations from bronchoalveolar lavage BAL fluid, biopsy, and autopsy samples derived, primarily, from severe cases.
FIG 4. Exacerbation of Preexisting Airway Diseases RSV is a major cause of exacerbation of airway diseases like asthma and chronic obstructive pulmonary disease COPD reviewed in references and RSV and Bacterial Colonization Airways that have been damaged by viral infections are susceptible to secondary bacterial infections Fig. FIG 5.
First-Generation Point-of-Care Tests First-generation point-of-care POC tests can be classified as direct antigen detection assays that required the user to make a visual discrimination of antigen detection and were generally based on chromogenic immunoassay technology.
Second-Generation POC Tests Recent antigen detection tests utilize specialized detection approaches to improve test characteristics. Clinical Laboratory versus POC Testing POC tests are often more rapid and convenient than tests that require sample submission to a clinical laboratory. Direct Fluorescent Antibody Testing Direct fluorescent antibody DFA testing requires a swab that allows for an appropriate number of epithelial cells to be collected and is largely applicable to appropriately collected nasopharyngeal specimens.
RSV Culture as a Nonbiased Option for Reference Laboratories Culture approaches, including shell vial culture approaches, have improved test characteristics compared to the second-generation POC assays e. Inhaled Nanobodies for Treatment of RSV Infection Perhaps a next generation of monoclonal antibody treatment for respiratory disease is the inhaled nanobody Experimental Antiviral Therapeutic Strategies A recent review provides an excellent summary of the challenges encountered in the development of RSV therapeutics Nucleoside Analogues and Small-Molecule Inhibitors From a historical perspective, nucleoside analogues that inhibit the function of the RSV polymerase are a rather obvious approach for the treatment of RSV infection.
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Signs and symptoms may include:. Infants are most severely affected by RSV. Signs and symptoms of severe RSV infection in infants include:. Most children and adults recover in one to two weeks, although some might have repeated wheezing. Severe or life-threatening infection requiring a hospital stay may occur in premature infants or in anyone who has chronic heart or lung problems. Seek immediate medical attention if your child — or anyone at risk of severe RSV infection — has difficulty breathing, a high fever, or a blue color to the skin, particularly on the lips and in the nail beds.
Respiratory syncytial virus enters the body through the eyes, nose or mouth. It spreads easily through the air on infected respiratory droplets. You or your child can become infected if someone with RSV coughs or sneezes near you. The virus also passes to others through direct contact, such as shaking hands. The virus can live for hours on hard objects such as countertops, crib rails and toys. Touch your mouth, nose or eyes after touching a contaminated object and you're likely to pick up the virus.
An infected person is most contagious during the first week or so after infection. But in infants and those with weakened immunity, the virus may continue to spread even after symptoms go away, for up to four weeks. By age 2, most children will have been infected with respiratory syncytial virus, but they can get infected by RSV more than once. Children who attend child care centers or who have siblings who attend school are at a higher risk of exposure and reinfection.
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