RSVRSVRespiratory Syncytial Respiratory Syncytial

VirusVirus

Sonia LengSonia LengHeather Leonard Heather Leonard

TaxonomyTaxonomy

OrderOrder MononegaviralesMononegavirales FamilyFamily ParamyzoviridaeParamyzoviridae Subfamily Subfamily PneumovirinaePneumovirinae GenusGenus PneumovirusPneumovirus

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Background Background Information of the Information of the VirusVirus

Enveloped virusEnveloped virus 150-200 nm 150-200 nm

diameterdiameter Helical Helical

nucleocapsidnucleocapsid (-) ssRNA(-) ssRNA

Most prevalent Most prevalent during winter during winter monthsmonths

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DiseasesDiseases

Bronchiolitis Bronchiolitis – droplet inhalation through the nosedroplet inhalation through the nose

AsthmaAsthma Pneumonia Pneumonia COPD COPD

– Chronic Obstructive Chronic Obstructive Pulmonary DiseasePulmonary Disease

Spread through respiratory Spread through respiratory secretionssecretions- coughing, sneezing- coughing, sneezing

Infection ProcessInfection Process

RSV envelope fuses to cell RSV envelope fuses to cell membrane and injects viral membrane and injects viral genome into the cell’s cytoplasm genome into the cell’s cytoplasm where translation will occur and where translation will occur and the virion will be replicatedthe virion will be replicated

Genome is transcribed from 3’ Genome is transcribed from 3’ end into monocistronic mRNA end into monocistronic mRNA moleculesmolecules– Each species only encodes a Each species only encodes a

single proteinsingle protein New viruses released via New viruses released via

buddingbudding Clumping may occur when new Clumping may occur when new

synthesized RSV surrounded by synthesized RSV surrounded by other infected cellsother infected cells

New viruses spread from cell to New viruses spread from cell to cellcell

produces a characteristic fusion produces a characteristic fusion of human cells in tissue cultureof human cells in tissue culture– the syncytial effect the syncytial effect www.bact.wisc.edu/.../ViralDisease.html

SymptomsSymptoms

Occurs within either days or hours of exposureOccurs within either days or hours of exposure vary from person to personvary from person to person symptoms most severe in children under the symptoms most severe in children under the

age of twoage of two symptoms in adults and children are mildsymptoms in adults and children are mild

– Stuffy NoseStuffy Nose– Nose flaringNose flaring– Low-grade feverLow-grade fever– WheezingWheezing– Rapid BreathingRapid Breathing– Ear InfectionEar Infection

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Diagnostic TestsDiagnostic Tests For confirmation of RSV, For confirmation of RSV,

proper testing of the proper testing of the patient's respiratory patient's respiratory secretions will: secretions will: – Positively identify RSV  Positively identify RSV  – Rule out bacterial Rule out bacterial

infection  infection  Nasopharyngeal Nasopharyngeal

secretions containing secretions containing epithelial cells are epithelial cells are necessary for positive necessary for positive diagnosis of severe RSV diagnosis of severe RSV infectionsinfections

There are two strains, A There are two strains, A and Band B– A causes severe casesA causes severe cases– B is asymptomatic and B is asymptomatic and

is transmitted to most is transmitted to most peoplepeoplehttp://www.rsvinfo.com/diagnosing/diagnosing.html

Treatment Treatment

Currently no RSV vaccine Currently no RSV vaccine availableavailable

No treatment given in mild No treatment given in mild

diseasedisease– just medication to reduce feverjust medication to reduce fever

Oxygen therapy and mechanical Oxygen therapy and mechanical ventilation (severe disease)ventilation (severe disease)

Ribavirin aerosol (severe disease)Ribavirin aerosol (severe disease)– Sometimes used---IGIV (immune globulin Sometimes used---IGIV (immune globulin

intravenous) with RSV-IGIV (neutralizing RSV intravenous) with RSV-IGIV (neutralizing RSV antibody) and Ribavirin. [severe disease]antibody) and Ribavirin. [severe disease]

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Treatment (cont.)Treatment (cont.)

Drug TherapiesDrug Therapies1.1. HRSV IV immune globulin (RSV-IVIG)HRSV IV immune globulin (RSV-IVIG)

First approved immunoprophylacticFirst approved immunoprophylactic released as Respigam (1996)released as Respigam (1996) made by high titre Sera (protective and neutralizing antibodies)made by high titre Sera (protective and neutralizing antibodies) administered monthly to prevent infection over 4-5 month administered monthly to prevent infection over 4-5 month

period. (during peak season)period. (during peak season)

2.2. Palvizumab (Synagis)Palvizumab (Synagis) next generation prophylacticnext generation prophylactic (MAb) humanized monoclonal antibody(MAb) humanized monoclonal antibody IM injection, not IVIM injection, not IV admin. During peak seasonadmin. During peak season

1960’s- Formalin-inactivated whole-virus hRSV vaccine 1960’s- Formalin-inactivated whole-virus hRSV vaccine given to infants (no previous exposure)given to infants (no previous exposure) later infected by hRSV, suffered severe symptoms of later infected by hRSV, suffered severe symptoms of

hRSV.hRSV.

PreventionPrevention

Frequent hand washingFrequent hand washing At-Risk children can be given an injection of RSV At-Risk children can be given an injection of RSV

antibodies monthly during peak season.antibodies monthly during peak season. Keeping school-age children away from younger Keeping school-age children away from younger

siblings (anyone under 2 years of age) if cold siblings (anyone under 2 years of age) if cold symptoms are presentsymptoms are present

Minimize number of visitors with the infantMinimize number of visitors with the infant Avoid any crowded places Avoid any crowded places

– mall, grocery storemall, grocery store If possible, don’t take child to daycare during If possible, don’t take child to daycare during RSV seasonRSV season Partake in influenza vaccinationsPartake in influenza vaccinations

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Epidemiology Epidemiology

TransmissionTransmission– RSV is easily transmitted via large, aerosolized RSV is easily transmitted via large, aerosolized

respiratory particles, or through contact with nasal respiratory particles, or through contact with nasal secretions, and may even be transmitted indirectly by secretions, and may even be transmitted indirectly by contact with contaminated objects, such as bathroom contact with contaminated objects, such as bathroom fixtures or even clothing. The most common sites of fixtures or even clothing. The most common sites of innoculation are the eyes and noseinnoculation are the eyes and nose

PrevalencePrevalence– Winter monthsWinter months– Most frequently transmitted between family members Most frequently transmitted between family members

and hospitalsand hospitals– The incubation period is three to five days for most The incubation period is three to five days for most

patientspatients– Strain A more prevalent than Strain B Strain A more prevalent than Strain B

Global DistributionGlobal Distribution– Warmer climates tend to have longer periods of Warmer climates tend to have longer periods of

outbreaks without any peak timesoutbreaks without any peak times– USA is generally November til MayUSA is generally November til May

Latest reports on Latest reports on morbidity and morbidity and mortality mortality Preventing Respiratory Syncytial Virus Preventing Respiratory Syncytial Virus

BronchiolitisBronchiolitis– mortality rate in the United States is at 0.13%mortality rate in the United States is at 0.13%

Viral Lower Respiratory Tract Infections in Viral Lower Respiratory Tract Infections in infants and Young Childreninfants and Young Children– mortality rate is increased when the child is mortality rate is increased when the child is

immunocompromised.immunocompromised.

Prospective study of healthcare utilization and Prospective study of healthcare utilization and respiratory morbidity due to RSV infection in respiratory morbidity due to RSV infection in prematurely born infantsprematurely born infants– RSV infection is associated with increased healthcare RSV infection is associated with increased healthcare

utilization and respiratory morbidity in premature babiesutilization and respiratory morbidity in premature babies– study was performed on infants born before 32 weeks study was performed on infants born before 32 weeks

gestation and during the RSV season of February through gestation and during the RSV season of February through September. Thereafter, they were followed until the September. Thereafter, they were followed until the corrected age of one.corrected age of one.

Latest research on Latest research on pathogenicity and pathogenicity and preventionprevention

PathogenicityPathogenicity– During the course of RSV infection, predominant T helper cell (TH) 2 During the course of RSV infection, predominant T helper cell (TH) 2

response is associated with disease progression, whereas predominant response is associated with disease progression, whereas predominant TH1 reaction provides response to physical sickness. Interleukin (IL)-18 TH1 reaction provides response to physical sickness. Interleukin (IL)-18 plays an important role in adjusting the TH1/TH2 immune response to plays an important role in adjusting the TH1/TH2 immune response to viral infections. The have tested the hypothesis that polymorphisms in IL-viral infections. The have tested the hypothesis that polymorphisms in IL-18 were associated with severe RSV-associated diseases. 18 were associated with severe RSV-associated diseases.

This study indicates possible involvement of IL-18 in the determination of This study indicates possible involvement of IL-18 in the determination of severe RSV-associated diseases. Defining the genetic basis of RSV bronchiolitis severe RSV-associated diseases. Defining the genetic basis of RSV bronchiolitis might help us in identifying new drug targets for a more specific therapy. might help us in identifying new drug targets for a more specific therapy.

PreventionPrevention– Palivizumab is approved for prevention of RSV disease, and ribavirin is Palivizumab is approved for prevention of RSV disease, and ribavirin is

approved for treatment of RSV infections but its efficacy in high-risk approved for treatment of RSV infections but its efficacy in high-risk patients has not been conclusively establishedpatients has not been conclusively established

31 (20 male and 11 female) patients hospitalized for RSV infection were treated 31 (20 male and 11 female) patients hospitalized for RSV infection were treated with intravenous palivizumab with intravenous palivizumab

– from October 2001 through July 2005from October 2001 through July 2005 25 patients (80%) also received ribavirin25 patients (80%) also received ribavirin 29 (93.6%) patients survived and 2 died29 (93.6%) patients survived and 2 died No adverse events attributed to palivizumab or ribavirin administration were No adverse events attributed to palivizumab or ribavirin administration were

observed. observed. Treatment of RSV-infected high-risk children with palivizumab alone or in Treatment of RSV-infected high-risk children with palivizumab alone or in

combination with ribavirin was well tolerated and associated with decreased combination with ribavirin was well tolerated and associated with decreased mortality compared with previous reportsmortality compared with previous reports

ReferencesReferences

Respiratory Syncytial VirusRespiratory Syncytial Virus. National Center for Infectious Diseases. Respiratory and Enteric Viruses Branch. 2005. National Center for Infectious Diseases. Respiratory and Enteric Viruses Branch. 2005http://www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htmhttp://www.cdc.gov/ncidod/dvrd/revb/respiratory/rsvfeat.htm

Respiratory Syncytial Virus.Respiratory Syncytial Virus. KidsHealth. 2006 KidsHealth. 2006http://www.kidshealth.org/parent/infections/lung/rsv.htmlhttp://www.kidshealth.org/parent/infections/lung/rsv.html

Prospective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infantsProspective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants. . S Broughton, A S Broughton, A Roberts, G Fox, E Pollina, M Zuckerman, S Chaudhry, and A Greenough. Thorax, Dec 2005; 60: 1039 - 1044.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?http://thorax.bmj.com/cgi/reprint/61/6/546?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Broughton&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=rmaxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Broughton&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCITelevance&resourcetype=HWCIT

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infantsDiminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. S Broughton, R Bhat, A Roberts, M . S Broughton, R Bhat, A Roberts, M Zuckerman, G Rafferty, and A Greenough. Zuckerman, G Rafferty, and A Greenough. Arch. Dis. ChildArch. Dis. Child. 2006; 91;26-30; 27 Sept 2005. 2006; 91;26-30; 27 Sept 2005http://adc.bmj.com/cgi/content/full/91/1/26?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=rmaxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Broughton&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCITelevance&resourcetype=HWCIT

Human Respiratory Syncytial Virus (HRSV).Human Respiratory Syncytial Virus (HRSV). Virology Down Under. Virus, Disease, Diagnosis. 2005 Virology Down Under. Virus, Disease, Diagnosis. 2005http://www.uq.edu.au/vdu/VDUHumanRespiratorySyncytialVirus.htmhttp://www.uq.edu.au/vdu/VDUHumanRespiratorySyncytialVirus.htm

Signs and Symptoms of Human Respiratory Syncytial Virus. About.com-Lung Diseases. 2006Signs and Symptoms of Human Respiratory Syncytial Virus. About.com-Lung Diseases. 2006http://lungdiseases.about.com/od/respiratorysyncytialviru1/a/symptoms_rsv.htmhttp://lungdiseases.about.com/od/respiratorysyncytialviru1/a/symptoms_rsv.htm

Respiratory Syncytial Virus Prevention. Respiratory Syncytial Virus Prevention. About.com-Lung Diseases. 2006 About.com-Lung Diseases. 2006http://lungdiseases.about.com/od/respiratorysyncytialviru1/a/rsv_prevention.htmhttp://lungdiseases.about.com/od/respiratorysyncytialviru1/a/rsv_prevention.htm

Preventing Respiratory Syncytial Virus Bronchiolitis. Preventing Respiratory Syncytial Virus Bronchiolitis. Mike Sharland and Alison Bedford-RussellMike Sharland and Alison Bedford-Russell BMJ BMJ 2001;322:62-63 2001;322:62-63http://www.bmj.com/cgi/content/full/322/7278/62?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&resoumaxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Preventing+Respiratory+Syncytial+Virus&searchid=1&FIRSTINDEX=0&resourcetype=HWCITrcetype=HWCIT

RSVRSV. The RSV Info Center. . The RSV Info Center. http://www.rsvinfo.com/index.htmlhttp://www.rsvinfo.com/index.html

Principle and Practices of Clinical VirologyPrinciple and Practices of Clinical Virology. Arie J. Zuckerman. John Wiley and Son Ltd. 2004. . 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=7g69QMY7qhttp://books.google.com/books?id=TDEsMa8Jp2EC&pg=PA325&lpg=PA325&dq=global+distribution+of+rsv&source=web&ots=7g69QMY7qd&sig=mIwi7HdAbiokeSean9JD_C6JOZo#PPA1,M1d&sig=mIwi7HdAbiokeSean9JD_C6JOZo#PPA1,M1

Viral Lower Respiratory Tract Infections in infants and Young Children. Viral Lower Respiratory Tract Infections in infants and Young Children. JBM van Woensel, WMC van Aalderen and JLL Kimpen. BMJJBM van Woensel, WMC van Aalderen and JLL Kimpen. BMJ 2003;327;36-402003;327;36-40

http://www.bmj.com/cgi/content/full/327/7405/36?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Viral+Lower+Respiratory+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=HWCITTract+Infection&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Interleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory syncytial virus infectionInterleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory syncytial virus infection. Puthothu B., et al. Center for . Puthothu B., et al. Center for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany. Pediatric Infectious Disease Journal. 2007 Dec;26(12):1094-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?8. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18043444&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanDb=pubmed&Cmd=ShowDetailView&TermToSearch=18043444&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumel.Pubmed_RVDocSum

Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patientsIntravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients. . Chávez-Bueno S., Chávez-Bueno S., et al. Department of Pediatrics, Division of Infectious Diseases, The University of Texas Southwestern Medical Center at Dallas, TX. Pediatric 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?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. Db=pubmed&Cmd=ShowDetailView&TermToSearch=18043443&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.

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