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

3. 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.

4. 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

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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. RSV:Clinical 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.

12. RSV; Clinical Manifestations • LRT disease: • Bronchiolitis VS. Pneumonia • Bronchiolitis & Pneumonia • Overwhelming Sepsis: • Young infants • Apnea: • Preterm infants • Croup: • Fewer than 10%

13. RSV : Clinical manifestations • High risk infants: • Preterm infants • Chronic lung disease • Congenital Heart disease • Immunocompromised • Neurological disorders • Multiple congenital Anomalies.

14. 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.

15. Complications & long term Effects: • Acute: • Respiratory Failure • Apnea • Secondary bacterial infection • Long Term Effects: • Reactive Airway Disease??

16. 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

17. 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.

18. RSV: Diagnosis…cont. • Infants: • Nasal wash • Children & adults: • Swab from nasal turbinates+pharynx • 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.

19. 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

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

21. 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

22. RSV Therapy: Ribavirin • AAP : Decisions regarding Ribavirin therapy are to be based on individual clinical situation & physician`s 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

23. RSV Therapy : Others • IV & inhaled Ig`s 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

24. Infection control Procedures During RSV season • Educate hospital staff & patient`s 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.

25. 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..

26. 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.

27. 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.

28. 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.

29. AAP Recommendations for prophylaxis : • Children< 2yeras ,chronic lung disease& received medical therapy in the last 6 months. • Infants < 32 wks gestation: • < 28 wks • 32 > age > 28 • 35> age >32

30. 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

31. 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.