Respiratory Syncytial Virus Concerns and Control

1
Respiratory Syncytial Virus Concerns and
Control

• Pediatrics in Review Vol. 24 No. 9
• Sept. 2003

2
Respiratory Syncytial Virus

• Introduction
• Virology
• Epidemiology
• Pathogenesis Immunity
• Complications Long term Effects
• Diagnosis
• Therapy Prevention

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RSV Introduction

• RSV is responsible for outbreaks of lower
  respiratory tract disease in young children.
• Bronchiolitis pneumonia from RSV are frequent
  causes of hospitalization.
• Recent conformation of the significance of RSV in
  causing respiratory tract illness throughout
  life.
• Therapy prevention based on increased
  understanding of the virus host response .
• Control of RSV infection.

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RSV Virology

• RSV Paramyxovirus, pneumovirus.
• RSV chimpanzee coryza agent.
• RSV Isolated from infants with respiratory
  symptoms , renamed because of its characteristic
  syncytial pattern.
• Enveloped virus, -ve single stranded RNA genome
• Genome codes for 10 m RNAs, each codes for a
  specific protein.
• Viral envelop F, G ,SH, M ,M2
• Neucleocapsid L, N, P
• NS1, NS2

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RSV Virology

• Two major groups A B
• PH 7.5, Temperature sensitive.
• Stable in hospital environment recovered
• from countertops rubber gloves.
• Nosocomial Pathogen

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RSV Epedemiology

• Present world wide, yearly epidemics.
• Appears in Nov. or Dec. persists till Apr. or
  May.
• A strain predominant , the two strains circulate.
• Strain variation does not significantly affect
  the clinical severity.
• Peak incidence 2-5 months.

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RSV Epidemiology

• In the 1st two years of life one or more RSV
  infections
• More severe Boys , lower socioeconomic classes.
• Reinfection throughout life is common.
• Milder than primary infection.

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RSV Pathogenesis Immunity

• Incubation period 2-8 days.
• Ocular, nasal contact with infected secretions.
• Upper airway cough rhinorrhea.
• 50 primary infection spreads to lower tract.
• Bronchiolitis lymphocyte infiltrate epithelial
  proliferation.
• Obstruction mucus epithelium .
• Hyperinflation.
• Interstitial infiltrates Pneumonia.

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RSV Immunity

• Immune response not well understood.
• Different parts of immune system are involved.
• Antibodies
• Higher levels of maternal Abs , lower infection
  rates.
• Prophylactic Abs reduce but do not eliminate
  severe disease.
• No level of serum Abs provides protection.
• Type of Ab generated may be critical.

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RSV Immunity

• Cell mediated immunity
• Integral in clearance recovery.
• T- cell deficiency severe infection prolonged
  shedding.
• Type of T-cell response influences control.
• Type extent of cytokine production determines
  response to RSV.

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RSVClinical Features

• Wide range of illness , rarely asymptomatic.
• Illness begins cough , nasal congestion
  fever.
• Ottitis Media
• LRT disease 50
• LRT disease tachypnea , dyspnea, retractions.
• Feeding difficulty, hypoxemia.

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RSV Clinical Manifestations

• LRT disease
• Bronchiolitis VS. Pneumonia
• Bronchiolitis Pneumonia
• Overwhelming Sepsis
• Young infants
• Apnea
• Preterm infants
• Croup
• Fewer than 10

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RSV Clinical manifestations

• High risk infants
• Preterm infants
• Chronic lung disease
• Congenital Heart disease
• Immunocompromised
• Neurological disorders
• Multiple congenital Anomalies.

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RSV Clinical manifestations Children Adults

• Repeated Infections milder , localized to URT.
• LRTI uncommon, may be followed by airway
  hyperactivity.
• Immunocompromised BMT severe , fatal disease
• URT symptoms suspect RSV
• Early therapeutic measures.

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Complications long term Effects

• Acute
• Respiratory Failure
• Apnea
• Secondary bacterial infection
• Long Term Effects
• Reactive Airway Disease??

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Diagnosis

• Young Children
• Season
• Typical history
• Physical examination
• Children Adults
• Signs Symptoms are less specific.
• Chest x ray nonspecific
• Chest X rays
• Hyperinflation
• Peribronchial thickening
• Increased interstitial markings
• Consolidation, Atelectasis

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RSV Diagnosis

• In children with mild disease, definitive
  diagnosis may not be necessary.
• In hospitalized patients those with severe
  disease ,an accurate diagnosis may limit further
  lab. evaluation and antibiotic use.
• RSV may be identified by viral isolation or by
  one of numerous rapid assays.

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RSV Diagnosiscont.

• Infants
• Nasal wash

• Children adults
• Swab from nasal turbinatespharynx
• or bronchoalveolar lavage are the most likely to
  be positive Specimens obtained by endotracheal
  tube
• Specimens for culture should be placed in viral
  culture media kept cold during transport.
• RSV grows in multiple cell lines ( Hep-2 HeLa)
• Typical pattern syncytial giant cell , 3-7
• Fluorescein-labled Ab are applied to cultures.

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RSV Diagnosis

• Rapid assays
• Fluorescent antibody tests
• Enzyme immunoassays
• Reverse transcriptase PCR
• Tissue Biopsies
• Serologic testing for RSV is not useful for
  management
• Has been used in epidemiological studies.
• Difficult to interpret in the very young
  immunocompromised

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RSV Therapy

• RSV therapy remains largely supportive
• Supplemental oxygen, IV fluids
• Bronchodilators??
• Corticosteroids??
• Vitamin A??

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RSV Ribavirin

• Ribavirin the only antiviral agent currently
  licensed for treatment of RSV infection.
• It is a synthetic nucleoside analog that
  interferes with expression of mRNA prtn
  synthesis.
• Nebulized Ribavirin is associated with clinical
  improvement,but a decrease in hospital stay has
  not been documented.
• Efficacy vs. Cost
• Toxicity adverse reactions
• Ventilated patients

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RSV Therapy Ribavirin

• AAP Decisions regarding Ribavirin therapy are
  to be based on individual clinical situation
  physicians experience
• Ribavirin is licensed for treatment by aerosol
  route by O2 hood, tent or mask until
  improvement.
• Usually 3-7 days, or longer in severe cases.
• No guidelines regarding administration to adults

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RSV Therapy Others

• IV inhaled Igs have bee used in small numbers
  but with no significant benefit.
• Immunocompromised patients , in combination with
  Ribavirin.
• Other Agents
• IM alpha 2a interferon
• Surfactant
• Rh-DNA ase
• Drugs affecting cytokine production alone or with
  others
• New Antiviral agents

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Infection control Procedures During RSV season

• Educate hospital staff patients families about
  RSV.
• Emphasize maintain good hand washing
  procedures.
• Use contact isolation for patients with RSV.
• Cohort children RSV infection.
• Identify RSV by using rapid accurate assays.
• Use mask for staff who have respiratory symptoms.

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Infection Control

• Cohort staff , if possible , to infected
  uninfected patients
• Limit visitors during RSV season.
• Postpone elective admissions for high risk
  patients in RSV season.
• Identify uninfected infants who may benefit from
  immunoprophylaxis..

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RSV Prevention

• Prophylactic Antibodies to RSV has been shown to
  decrease severe disease.
• Two products have been approved for use in
  selected children at high risk for RSV.
• Neither product currently is licensed for use in
  infants with cyanotic congenital heart disease.
• Prophylaxis may be beneficial in
  Immunocompromised children.
• Expenses of prophylaxis.
• Regional analysis is required.
• Impact on long term complications is yet unknown.

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RSV Prevention RSV IGIV

• Approved in 1996, after multicenter PREVENT
  trial.
• Patients received monthly infusions of RSV-IVIG,
  or placebo during RSV season.
• Those receiving RSV-IVIG had a 41 reduction in
  rate of hospitalization,fewer hospital days
  less frequent O2 requirements.

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RSV Prevention Palivizumab

• It is a humanized IgG-1 monoclonal Ab, that binds
  to the F prtn of RSV.
• It is estimated to have 50 - 100X more activity
  than RSV IGIV.
• Given IM.
• Approved in 1998 after placebo controlled
  multicenter trial ( Impact Study)
• Administration resulted in 55 reduction in
  hospitalizations.
• RSV IVIG vs. Palivizumab.

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AAP Recommendations for prophylaxis

• Childrenlt 2yeras ,chronic lung disease received
  medical therapy in the last 6 months.
• Infants lt 32 wks gestation
• lt 28 wks
• 32 gt age gt 28
• 35gt age gt32

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RSV prevention Vaccines

• Development of an effective vaccine remains a
  challenge.
• A variety of approaches to Vaccine development
  have been studied.
• Types of candidate vaccines include inactivated
  ,live attenuated subunit vaccines.
• Successful immunization against RSV may require
  different individualized approaches.
• Maternal immunization may be protective , but not
  for LBW infants

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RSV prevention

• Additional strategies are needed to provide
  protection shortly after birth.
• In older individuals vaccines that the existing
  to RSV maybe beneficial or more feasible to
  develop.
• Possible therapeutic preventive measures are
  evolving rapidly, portending that the burden of
  RSV disease soon may be lessened.