Respiratory Respiratory SyncytialSyncytial Virus Virusinfectionsinfections

Dr.T.V.Rao MDDr.T.V.Rao MD

Discovery of Respiratory Discovery of Respiratory SyncytialSyncytial Virus Virus

In 1956, Morris and colleagues initially isolated In 1956, Morris and colleagues initially isolated RSV from chimpanzees with upper respiratory RSV from chimpanzees with upper respiratory tract (URT) infections as the causative agent of tract (URT) infections as the causative agent of most epidemic most epidemic Bronchiolitis Bronchiolitis cases. cases. Subsequently, Channock et al associated this Subsequently, Channock et al associated this agent with Bronchiolitis and LRT infection in agent with Bronchiolitis and LRT infection in infants. Since then, multiple epidemiologic infants. Since then, multiple epidemiologic studies have confirmed the role of this virus as studies have confirmed the role of this virus as the leading cause of LRT infection in infants and the leading cause of LRT infection in infants and young children. young children.

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RS virus major cause of RS virus major cause of Respiratory Infections.Respiratory Infections.

Human respiratoryHuman respiratory SyncytialSyncytial virus virus (RSV) was quickly (RSV) was quickly determined to be of determined to be of human origin and human origin and was shown to be the was shown to be the leading worldwide leading worldwide viral agent of serious viral agent of serious paediatric respiratory paediatric respiratory tract diseasetract disease. .

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RSV – Viral structureRSV – Viral structure RSV is Plemomorphic and RSV is Plemomorphic and

ranges in size from 150 – ranges in size from 150 – 300nm300nm

The viral envelope has two The viral envelope has two glycoprotein's- the G protein glycoprotein's- the G protein by which the virus attaches to by which the virus attaches to cell surfaces, and fusion (F) cell surfaces, and fusion (F) protein which brings about protein which brings about fusion between viral and host fusion between viral and host cell membranes.cell membranes.

The The F proteinF protein is also is also responsible for cell to cell responsible for cell to cell fusion, which is responsible fusion, which is responsible for for typical syncytial typical syncytial cytopathiccytopathic changes in RSV changes in RSV infection.infection.

RespiratoryRespiratory SyncytialSyncytial virusvirus RespiratoryRespiratory syncytialsyncytial

virusvirus (RSV) is a leading (RSV) is a leading cause of severe cause of severe respiratoryrespiratory infection in infection in infants and children. infants and children. RSV is an RNA RSV is an RNA virusvirus whose genome encodes whose genome encodes 10 proteins. The G 10 proteins. The G protein is responsible for protein is responsible for viral attachment to cells viral attachment to cells whilst the F protein whilst the F protein promotes syncytia promotes syncytia formation. formation.

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Differs from ParamyxovirusesDiffers from Paramyxoviruses

Unlike Paramyxoviruses it does not posses Unlike Paramyxoviruses it does not posses Haemagglutinnin activity.Haemagglutinnin activity.

Do not posses neuraminidase or hemolytic Do not posses neuraminidase or hemolytic propertiesproperties

The size of nucelocapsid diameter is less than The size of nucelocapsid diameter is less than Paramyxoviruses.Paramyxoviruses.

RS virus are placed in a separate Genus RS virus are placed in a separate Genus PneumovirusPneumovirus

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RS virus do not withstand RS virus do not withstand freezingfreezing

The virus is relatively The virus is relatively fragile and may not fragile and may not survive even snap –survive even snap –freezing at -70freezing at -7000cc

Specimens for Specimens for isolation should isolation should not be frozennot be frozen

Propagation of RSVPropagation of RSV

It can be propagated It can be propagated in in He LaHe La and Hep-2 and Hep-2 cell culture lines.cell culture lines.

Highly labile virus Highly labile virus and promptly and promptly inactivated at room inactivated at room temperatures temperatures

Sero typing of Respiratory Sero typing of Respiratory Syncytial virusSyncytial virus

For all practical purposes For all practical purposes there is only there is only one serotypeone serotype

With the use of monoclonal With the use of monoclonal antibodies that there are antibodies that there are two subtypes A and B two subtypes A and B strainsstrains. .

In Newcastle upon In Newcastle upon Tyne, strains of Tyne, strains of subtype A have been subtype A have been prevalent every year prevalent every year since 1974since 1974

But subgroup B strains were But subgroup B strains were erratic and have not been erratic and have not been isolated every winter.isolated every winter.

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Infects Animals tooInfects Animals too

RS virus infects cattle RS virus infects cattle and and chimpanzeeschimpanzees

Both goats and Both goats and sheep may be sheep may be infected naturallyinfected naturally

Even rodents can be Even rodents can be adopted after some adopted after some adoption.adoption.

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Majority of Children are InfectedMajority of Children are Infected

Almost all children Almost all children will be infected with will be infected with RSV by their second RSV by their second birthday. birthday.

RSV causes RSV causes respiratory illness in respiratory illness in infants and young infants and young children, and is the children, and is the most important cause most important cause of Bronchiolitis. of Bronchiolitis.

RS virus is major cause of RS virus is major cause of Respiratory Infection - GloballyRespiratory Infection - Globally

Respiratory Syncytial virus (RSV) is recognized Respiratory Syncytial virus (RSV) is recognized as the most important cause of serious lower as the most important cause of serious lower respiratory tract illness in infants and young respiratory tract illness in infants and young children worldwide causing repeat infections children worldwide causing repeat infections throughout life with serious complications throughout life with serious complications occurring in the elderly and immune occurring in the elderly and immune compromised patient.compromised patient.

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Involvement of Alveoli and Alveolar Involvement of Alveoli and Alveolar space - A significant featurespace - A significant feature

Major areas of Infection in RS Major areas of Infection in RS virusesviruses

Clinical diagnosis will Clinical diagnosis will be supported with be supported with presence of RS virus presence of RS virus in the Nasopharynx in the Nasopharynx and there is clinical and there is clinical evidence of lower evidence of lower respiratory tract respiratory tract involvement.involvement.

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Clinical FeaturesClinical Features The peak incidence is in The peak incidence is in

those under 1 year of those under 1 year of age.age.

The most serious illness The most serious illness manifest with manifest with BronchiolitisBronchiolitis in young in young babiesbabies

Leads to hyperinflation of Leads to hyperinflation of lungs secondary to lungs secondary to bronchiolar inflamation bronchiolar inflamation acting as a on way valve.acting as a on way valve.

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Patients with respiratory syncytial virus (RSV) Patients with respiratory syncytial virus (RSV)

may present with the following may present with the following SymptomsSymptoms:: Fever (typically low-Fever (typically low-

grade)grade) CoughCough TachypneaTachypnea CyanosisCyanosis RetractionsRetractions WheezingWheezing RalesRales

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Can be Life ThreateningCan be Life Threatening

The RS viral infection The RS viral infection is potentially in those is potentially in those with or congenital with or congenital heart disease heart disease Bronchopulmonary Bronchopulmonary dysplasia defects, or dysplasia defects, or in those who are in those who are Immunosupressed or Immunosupressed or Immunodeficient.Immunodeficient.

Sudden Infant Death syndromeSudden Infant Death syndrome( SIDS )( SIDS )

RS virus has been RS virus has been recovered from some recovered from some victims of the Sudden victims of the Sudden infant death infant death syndromesyndrome

Although it may have Although it may have been contributed to been contributed to death, other factor death, other factor are also significantly are also significantly contributed.contributed.

Active Clinical manifestationsActive Clinical manifestations

The majority of infected present with The majority of infected present with clinical features of clinical features of BronchiolitisBronchiolitis

In majority of cases recovery is complete.In majority of cases recovery is complete. In older children, and adults the virus In older children, and adults the virus

cause minor illness,cause minor illness, Reinfections are common and in adults Reinfections are common and in adults

may cause no more than coldmay cause no more than cold..

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RS virus infections can RS virus infections can predispose to….predispose to….

Some reports suggest the Some reports suggest the infection can predispose infection can predispose to Chronic respiratory to Chronic respiratory tract disease, tract disease, Asthma,Bronchectasis Asthma,Bronchectasis etcetc

Several studies in Several studies in progress to prove the progress to prove the predisposition with predisposition with

RS virusRS virus

RS virus can infect old aged RS virus can infect old aged groupsgroups

There are upcoming reports of severe illness There are upcoming reports of severe illness with some fatalities in old people’s homes as with some fatalities in old people’s homes as well as in elderly living in a communitywell as in elderly living in a community

The under diagnosis can be attributed lack The under diagnosis can be attributed lack of confirming Virological diagnosis in adults of confirming Virological diagnosis in adults and elderly.and elderly.

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Factors have been associated with Factors have been associated with

increasedincreased risk of acquiring RSV disease,risk of acquiring RSV disease, Attending child care centres.Attending child care centres. Older siblings in preschool or schoolOlder siblings in preschool or school Exposure to environmental pollutants (eg, Exposure to environmental pollutants (eg,

cigarette smoke)cigarette smoke) Multiple birth sets (especially triplets or Multiple birth sets (especially triplets or

greater)greater) Minimal breastfeedingMinimal breastfeeding

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Other contributing factors in Other contributing factors in Respiratory syncitical virus InfectionRespiratory syncitical virus Infection

Premature children , especially birth at less than 35 Premature children , especially birth at less than 35 weeks' gestation weeks' gestation

Age younger than 3 months at time of infectionAge younger than 3 months at time of infection Chronic lung diseaseChronic lung disease Congenital heart diseaseCongenital heart disease Toxic appearance at time of presentationToxic appearance at time of presentation Respiratory rate more than 70 per minute in room airRespiratory rate more than 70 per minute in room air Atelectasis and/or pneumonitis on chest radiographyAtelectasis and/or pneumonitis on chest radiography Oxygen less than 95% on room airOxygen less than 95% on room air

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Laboratory Diagnosis of RS viral Laboratory Diagnosis of RS viral infectioninfection..

Viral detection and Viral detection and IsolationIsolation

In acute phase virus In acute phase virus may be may be demonostrated by demonostrated by ImmunofluorescencImmunofluorescence,e, Enzyme immunoEnzyme immuno assaysassays and and CultureCulture

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Rapid Diagnosis in RS Viral Rapid Diagnosis in RS Viral infectionsinfections

In acute phase of illness, In acute phase of illness, a Rapid diagnosis in > a Rapid diagnosis in > than 1 hour by than 1 hour by Immunofluorescence Immunofluorescence with conjugated with conjugated monoclonal antibodiesmonoclonal antibodies with adequate number of with adequate number of desquamated respiratory desquamated respiratory cell is reliable.cell is reliable.

However antigen However antigen detection and culture detection and culture methods are good for methods are good for diagnosing RS virus diagnosing RS virus infection in infants and infection in infants and young children.young children.

SerologySerology

Serological assessment Serological assessment using complement using complement fixation is generally not fixation is generally not helpful.helpful.

Immunoassays for G and Immunoassays for G and F proteins may offer F proteins may offer more reliable serological more reliable serological tests, in adults where tests, in adults where other options are limited.other options are limited.

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Molecular Methods in RS viral Molecular Methods in RS viral infectioninfection

The emerging The emerging molecular methods molecular methods such as reverse such as reverse transcription-transcription-polymerase chain polymerase chain reaction, either for a reaction, either for a single virus or single virus or multiplexed to detect multiplexed to detect a panel of virusesa panel of viruses

TreatmentTreatment

A supportive management with tube A supportive management with tube feeding in cases of difficulty in sucklingfeeding in cases of difficulty in suckling

Use of oxygen if indicated.Use of oxygen if indicated. RibavirinRibavirin is a specific antiviral drug, is a specific antiviral drug,

proved to effective when given as a small proved to effective when given as a small particle aerosol although it is apparently particle aerosol although it is apparently not effective intravenous infusion.not effective intravenous infusion.

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Indication for ChemotherapyIndication for Chemotherapy

The chemotherapy with Ribavirin is expensive and its The chemotherapy with Ribavirin is expensive and its recommended use is confined to those babies who are recommended use is confined to those babies who are at risk from rampant RS virus, because they have at risk from rampant RS virus, because they have congenital heart or lung abnormalitiescongenital heart or lung abnormalities

The use os Hyper immune RS virus immunoglobulin The use os Hyper immune RS virus immunoglobulin and humanized monoclonal antibodies have become and humanized monoclonal antibodies have become available for treatment and prevention of RS infection. available for treatment and prevention of RS infection. In view of higher costs they are warranted in selected In view of higher costs they are warranted in selected infants born with low birth weight or preexisting infants born with low birth weight or preexisting bronchopulmonary dysplasiabronchopulmonary dysplasia

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Epidemics and Seasonal Epidemics and Seasonal VariationVariation

In temperate climates in both the northern and In temperate climates in both the northern and southern hemisphere, RS virus causes a southern hemisphere, RS virus causes a substantial winter epidemic every year.substantial winter epidemic every year.

In tropical regions the epidemics manifest in hot In tropical regions the epidemics manifest in hot periods of summer. periods of summer.

However sporadic cases occur throughout the However sporadic cases occur throughout the yearyear

The RS virus produces infections all over the The RS virus produces infections all over the worldworld

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Vaccine - FailuresVaccine - Failures A formalin inactivated crude, A formalin inactivated crude,

whole virus vaccine was tried whole virus vaccine was tried in 1960, but failed to produce in 1960, but failed to produce immunity in the recipientsimmunity in the recipients

The difficulties in preparing The difficulties in preparing safe vaccine for RSV lie with safe vaccine for RSV lie with young and immunologically young and immunologically immature recipients.immature recipients.

Yet to date there is safe Yet to date there is safe vaccine avialble for vaccine avialble for universal useuniversal use

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Created for awarness on Created for awarness on Respiratory Syncytial Respiratory Syncytial

Viral Infections in Viral Infections in Developing worldDeveloping world

Dr.T.V.Rao MDDr.T.V.Rao MD

EmailEmaildoctortvrao@gmail.comdoctortvrao@gmail.com