RSV

1. RSV Respiratory Syncytial Virus Sonia Leng Heather Leonard

2. Taxonomy • Order Mononegavirales • Family Paramyzoviridae • Subfamily Pneumovirinae • Genus Pneumovirus www.virologyj.com/content/3/1/34/figure/F3

3. Background Information of the Virus • Enveloped virus • 150-200 nm diameter • Helical nucleocapsid • (-) ssRNA • Most prevalent during winter months www.med.sc.edu

4. Diseases • Bronchiolitis • droplet inhalation through the nose • Asthma • Pneumonia • COPD • Chronic Obstructive Pulmonary Disease Spread through respiratory secretions - coughing, sneezing

5. Infection Process • RSV envelope fuses to cell membrane and injects viral genome into the cell’s cytoplasm where translation will occur and the virion will be replicated • Genome is transcribed from 3’ end into monocistronic mRNA molecules • Each species only encodes a single protein • New viruses released via budding • Clumping may occur when new synthesized RSV surrounded by other infected cells • New viruses spread from cell to cell • produces a characteristic fusion of human cells in tissue culture • the syncytial effect www.bact.wisc.edu/.../ViralDisease.html

6. Symptoms • Occurs within either days or hours of exposure • vary from person to person • symptoms most severe in children under the age of two • symptoms in adults and children are mild • Stuffy Nose • Nose flaring • Low-grade fever • Wheezing • Rapid Breathing • Ear Infection www.istockphoto.com/file_closeup/

7. Diagnostic Tests • For confirmation of RSV, proper testing of the patient's respiratory secretions will: • Positively identify RSV  • Rule out bacterial infection  • Nasopharyngeal secretions containing epithelial cells are necessary for positive diagnosis of severe RSV infections • There are two strains, A and B • A causes severe cases • B is asymptomatic and is transmitted to most people http://www.rsvinfo.com/diagnosing/diagnosing.html

8. Treatment • Currently no RSV vaccine available • No treatment given in mild disease • just medication to reduce fever • Oxygen therapy and mechanical ventilation (severe disease) • Ribavirin aerosol (severe disease) • Sometimes used---IGIV (immune globulin intravenous) with RSV-IGIV (neutralizing RSV antibody) and Ribavirin. [severe disease] www.krockathon.com/index.php?module=rules

9. Treatment (cont.) • Drug Therapies 1. HRSV IV immune globulin (RSV-IVIG) • First approved immunoprophylactic • released as Respigam (1996) • made by high titre Sera (protective and neutralizing antibodies) • administered monthly to prevent infection over 4-5 month period. (during peak season) 2. Palvizumab (Synagis) • next generation prophylactic • (MAb) humanized monoclonal antibody • IM injection, not IV • admin. During peak season • 1960’s- Formalin-inactivated whole-virus hRSV vaccine • given to infants (no previous exposure) • later infected by hRSV, suffered severe symptoms of hRSV.

10. Prevention • Frequent hand washing • At-Risk children can be given an injection of RSV antibodies monthly during peak season. • Keeping school-age children away from younger siblings (anyone under 2 years of age) if cold symptoms are present • Minimize number of visitors with the infant • Avoid any crowded places • mall, grocery store • If possible, don’t take child to daycare during RSV season • Partake in influenza vaccinations www.victorystore.com/.../washhands.htm

11. Epidemiology • Transmission • RSV is easily transmitted via large, aerosolized respiratory particles, or through contact with nasal secretions, and may even be transmitted indirectly by contact with contaminated objects, such as bathroom fixtures or even clothing. The most common sites of innoculation are the eyes and nose • Prevalence • Winter months • Most frequently transmitted between family members and hospitals • The incubation period is three to five days for most patients • Strain A more prevalent than Strain B • Global Distribution • Warmer climates tend to have longer periods of outbreaks without any peak times • USA is generally November til May

12. Latest reports on morbidity and mortality • Preventing Respiratory Syncytial Virus Bronchiolitis • mortality rate in the United States is at 0.13% • Viral Lower Respiratory Tract Infections in infants and Young Children • mortality rate is increased when the child is immunocompromised. • Prospective study of healthcare utilization and respiratory morbidity due to RSV infection in prematurely born infants • RSV infection is associated with increased healthcare utilization and respiratory morbidity in premature babies • study was performed on infants born before 32 weeks gestation and during the RSV season of February through September. Thereafter, they were followed until the corrected age of one.

13. Latest research on pathogenicity and prevention • Pathogenicity • During the course of RSV infection, predominant T helper cell (TH) 2 response is associated with disease progression, whereas predominant TH1 reaction provides response to physical sickness. Interleukin (IL)-18 plays an important role in adjusting the TH1/TH2 immune response to viral infections. The have tested the hypothesis that polymorphisms in IL-18 were associated with severe RSV-associated diseases. • This study indicates possible involvement of IL-18 in the determination of severe RSV-associated diseases. Defining the genetic basis of RSV bronchiolitis might help us in identifying new drug targets for a more specific therapy. • Prevention • Palivizumab is approved for prevention of RSV disease, and ribavirin is approved for treatment of RSV infections but its efficacy in high-risk patients has not been conclusively established • 31 (20 male and 11 female) patients hospitalized for RSV infection were treated with intravenous palivizumab • from October 2001 through July 2005 • 25 patients (80%) also received ribavirin • 29 (93.6%) patients survived and 2 died • No adverse events attributed to palivizumab or ribavirin administration were observed. • Treatment of RSV-infected high-risk children with palivizumab alone or in combination with ribavirin was well tolerated and associated with decreased mortality compared with previous reports

14. References • Respiratory Syncytial Virus. National Center for Infectious Diseases. Respiratory and Enteric Viruses Branch. 2005 http://www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htm • Respiratory Syncytial Virus. KidsHealth. 2006 http://www.kidshealth.org/parent/infections/lung/rsv.html • Prospective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants. S Broughton, A Roberts, G Fox, E Pollina, M Zuckerman, S Chaudhry, and A Greenough. Thorax, Dec 2005; 60: 1039 - 1044. http://thorax.bmj.com/cgi/reprint/61/6/546?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Broughton&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT • Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. S Broughton, R Bhat, A Roberts, M Zuckerman, G Rafferty, and A Greenough. Arch. Dis. Child. 2006; 91;26-30; 27 Sept 2005 http://adc.bmj.com/cgi/content/full/91/1/26?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Broughton&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT • Human Respiratory Syncytial Virus (HRSV). Virology Down Under. Virus, Disease, Diagnosis. 2005 http://www.uq.edu.au/vdu/VDUHumanRespiratorySyncytialVirus.htm • Signs and Symptoms of Human Respiratory Syncytial Virus. About.com-Lung Diseases. 2006 http://lungdiseases.about.com/od/respiratorysyncytialviru1/a/symptoms_rsv.htm • Respiratory Syncytial Virus Prevention. About.com-Lung Diseases. 2006 http://lungdiseases.about.com/od/respiratorysyncytialviru1/a/rsv_prevention.htm • Preventing Respiratory Syncytial Virus Bronchiolitis. Mike Sharland and Alison Bedford-Russell BMJ 2001;322:62-63 http://www.bmj.com/cgi/content/full/322/7278/62?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Preventing+Respiratory+Syncytial+Virus&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT • RSV. The RSV Info Center. http://www.rsvinfo.com/index.html • Principle and Practices of Clinical Virology. Arie J. Zuckerman. John Wiley and Son Ltd. 2004. http://books.google.com/books?id=TDEsMa8Jp2EC&pg=PA325&lpg=PA325&dq=global+distribution+of+rsv&source=web&ots=7g69QMY7qd&sig=mIwi7HdAbiokeSean9JD_C6JOZo#PPA1,M1 • Viral Lower Respiratory Tract Infections in infants and Young Children. JBM van Woensel, WMC van Aalderen and JLL Kimpen. BMJ2003;327;36-40 http://www.bmj.com/cgi/content/full/327/7405/36?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Viral+Lower+Respiratory+Tract+Infection&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT • Interleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory syncytial virus infection. Puthothu B., et al. Center for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany. Pediatric Infectious Disease Journal. 2007 Dec;26(12):1094-8. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18043444&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum • Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients. Chávez-Bueno S., et al. Department of Pediatrics, Division of Infectious Diseases, The University of Texas Southwestern Medical Center at Dallas, TX. Pediatric Infectious Disease Journal. 2007 Dec;26(12):1089-93. ttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18043443&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.

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