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A. 5 month former 34 weeker who attends day care and has a 5 yo brother B. 11 month former 27 weeker C. 7 month former 31 weeker D. 18 month patient with cystic fibrosis on home 02 E. 14 month Tetrology of Fallot patient F. 22 month former 32 weeker with BPD who required diuretics and steroids in October,R3R3g"A 9 Background GRespiratory syncytial virus (RSV) is the primary cause of lower respiratory tract illness in young children. Generally resolves uneventfully in otherwise healthy children. High risk populations may develop severe and sometimes fatal lower respiratory tract infections. RSV infection annually contributes up to 126,300 pediatric hospitalizations in the U.S. Estimated annual hospitalization costs for RSV pneumonia in children <=4 years: $300 - $400 million (1998 $), now much greater. Annual mortality due to RSV in infants and children is estimated to range from 200 to over 2,700.HZHMicrobiology BasicsRSV is single-stranded RNA virus of Paramyxoviridae family Two subtypes, A and B A subtypes cause more disease Within subtypes are several genotypes Strains have shifts each year, accounting for reinfections BQD;QD<,$   Prematurity  @Prematurity increases risk of severe RSV infection. :4 23  ! Epidemiology Worldwide RSV epidemics occur yearly United States: November  April Peak: January  March (most areas) Peak: 2  3 months earlier (Southeast) 80% RSV admissions occur within 4 months of discharge from NICU.b%ZpZAZ% O"A   TransmissionMInoculation of nasal or ocular membranes after contact with virus containing secretions or fomites Virus can survive for several hours on hands and fomites (WASH HANDS!!!) Direct contact most common, large aerosol drops also implicated Incubation is 2-8 days Patients usually shed 3-8 days but can shed up to 4 weeks in young infantsNZN,[2ImmunityAlmost everyone has been infected with RSV by age 3 Does not convey total protection against reinfection Can be infected more than once in same RSV season but usually 2d infection milder Transplacental Ab does not protect completely against infection but high Ab s imply milder disease and usually is only in upper respiratory tractMMP] S8E Pathologic findings+Necrosis of epithelial cells Proliferation of bronchiolar epithelium Infiltrates of monocytes and T cells around arterioles Neutrophils between vasculature and small airways Leads to airway obstruction, air trapping, increased airway resistance Increased incidence of wheezing as children grow older,Z,,T  Hospital therapy for RSVCare is mainly supportive (fluids, respiratory support) Trial (one dose) of beta-agonist if bronchospasm. D/C if not improvement Steroids not recommended Ribavirin not recommended unless severe LRT infection Neither RSVIG nor Synagis is effective in treatment of hospitalized children Z>\ 3 ?5 RSVIG&Was developed as hyperimmune globulin from donors with high titers of RSV antibody In trials reduced hospitalizations in high risk infants by 41-63% Increased morbidity and mortality in CHD patients Interfered with immune response to live vaccines (MMR and varicella) No longer used frequently '',  ) Palivizumab (Synagis)$ Is monoclonal antibody (not blood product) against RSV F glycoprotein Easier to administer than RSVIG Does not interfere with response to live vaccines A newer but similar product is MEDI-524 or Numax More potent in animal trials Currently undergoing clinical evaluation*ZFZFG"Synagis  Synagis is available in 50 and 100 mg vials The cost is $725 per 50 mg and $1370 per 100 mg vial Synagis has a shelf life of 6 hours making drug wastage nearly inevitable *,pxpZ,  [  I Dosing of Synagis 15 mg/kg IM once per month for 5 doses Begin before RSV season begins, October or November Once dosing begins, continue even if patient is past age of indication Continue even if breakthrough infection  EfficacyIMpact-RSV trial in BPD pts and preemies 55% reduction in RSV-associated hospitalizations vs placebo Trial in CHD pts 45% fewer hospitalizations 73% fewer hospital days needing O2 56% fewer total hospital days Trial in 421 preemies without CLD who received Synagis or placebo 50% fewer infants in Synagis group had recurrent wheezing Shows that prevention of RSV LRTI may reduce risk of recurrent wheezing in preemies without CLD )P<PP]PBPPP)<]BHT!."Risk factors for severe disease,Less than 6 months Born during first half of RSV season Attending daycare Underlying lung disease Born before 35 weeks Congenital heart disease Immunocompromised patients SCIDS, leukemia, BM transplant Significant asthma (any age) Living at altitudes greater than 8000 feet Institutionalized elderly tP7PaPPcP7ac/#Adverse ReactionsjExtremely safe, no serious adverse events in two consecutive seasons seen Severe hypersensitivity (less than 1 per 100,000) About 1 per 100 children will have anti-Synagis antibodies and antibody response declines with continued dosing No resistance to Synagis by RSV seen Doesn t interfere with immunizations6Z6,R20%Specific RecommendationsBPD- younger than 2 yo needing medical therapy for lungs who required medical therapy within 6 mos of RSV season CHD  under 2 who have hemodynamically significant CHD Prematurity d" 28 weeks, younger than 1 yr at start of season 29-35 wks, younger than 6 mos 32-35 consider for infants <6 mos if 2 risk factors (day care attendance, congenital abnormalities, NMD, school-aged sibs) Immunocompromised  no controlled studies but seems apparent that those with SCIDS or HIV with low CD4 undergoing chemotherapy or post-transplant would benefit Structural or functional lung disease (such as CF) are at increased risk; no data on effectivenessTPPP"  I& LZ=(Medicaid and Synagis vSynagis is a benefit under the Comprehensive Care Program, under TH Steps Administered by a Synagis provider Eligibility for children under 2 the same except: Hemodynamically significant heart disease is defined as including: Pulmonary hypertension Digoxin or diuretics Oxygen Lung disease qualifies if: On steroids, diuretics, ventilator or 02 Transplants patients qualify PCP3PP)PPPC3)  HU<Kw<'Other considerationsjSocial issues (long distances from hospital) Home administration is preferred since may improve adherence    RSV Vaccine$Many challenges for effective vaccine Immature immunity Possible suppression of immune response by maternal antibody Several antigenically divergent strains Live attenuated vaccines are being tested Must be very attenuated in this young group However, lessens chance of detectable Ab responseT&ZwZ*Z^Z&w*^,}  >) Post-test Which of the following children should receive RSV prophylaxis during RSV season? A. 5 month former 34 weeker who attends day care and has a 5 yo brother B. 11 month former 27 weeker C. 7 month former 31 weeker D. 18 month patient with cystic fibrosis on home 02 E. 14 month Tetrology of Fallot patient F. 22 month former 32 weeker with BPD who was required diuretics and steroids in October,R7R7g"A =Answer to Pretest Question  ReferencesUp To Date,  Treatment and Prevention of RSV AAP Clinical Practice Guidelines,  Diagnosis and Management of Bronchiolitis , PEDIATRICS Volume 118, Number 4, October 2006 AAP Policy Statement, Revised Indications for the Use of Palivizumab and Respiratory Syncytial Virus Immune Globulin Intravenous for the Prevention of Respiratory Syncytial Virus Infections *jPm j  E /#$%&*+,4579:;? 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S \ 6D _P   P*   \ 6 _   R*  H \ 0޽h ? 3380___PPT10.VҠe0 |t  (  x  c $rB*p  r  S tC `    n  C FA,Healthybronchioletubet.d  C <A"prodshot_synagisH  0޽h ? 33___PPT10i.V='+D=' = @B + 0 8*(  8x 8 c $%C `}   r 8 S DpD `  H 8 0޽h ? 33___PPT10i.VY)+D=' = @B +n 0 % y(  ~  s *xC `}   ~  s *ܩD `    NФ?"pUp A: )"0  3H  0޽h ? ̙33y___PPT10Y+D=' = @B + 0 P*(  x  c $XC `}   r  S D `  H  0޽h ? 33___PPT10i.VB+D=' = @B +g 0 % zr (  ~  s *C `}   ~  s *D}?.     N?"0kkH H"0 3    `A Y? 8 Y$D0  H @j 4RSV Hospitalization Rate by Gestational Age at Birth"5  5 5  H  0޽h ? ̙33y___PPT10Y+D=' = @B + 0 % 9(  ~  s *09C `}   ~  s *9DHp     `A Z?  8 Z$D0I  H;    cRespiratory Illness Hospitalization Rate by Month of Discharge from NICU in Infants <= 32 Weeks GA"d  d d    NlD?"0 H"0 3 H  0޽h ? ̙33y___PPT10Y+D=' = @B + 0 `*(  x  c $ YC `}   r  S YD `P  H  0޽h ? 33___PPT10i.Vj+D=' = @B + 0 p*(  x  c $MC `}   r  S XfD `   H  0޽h ? 33___PPT10i.V@0+D=' = @B + 0  (   x  c $4tC`   r  S  uD `  T  C ,Arsv-cpe2H  0޽h ? 33___PPT10i.Vp9+D=' = @B + 0 D*(  Dx D c $C `}   r D S ЂD `  H D 0޽h ? 33___PPT10i.V]+D=' = @B + 0 (*(  (x ( c $؍C `}   r ( S D `  H ( 0޽h ? 33___PPT10i.V1!+D=' = @B +} 0 $(  r  S ؞C `}   r  S D `  H  0޽h ? h___PPT10i.W`(Z+D=' = @B +u 0 % @(  ~  s *C `}   ~  s *D `    Nl?"p9p H"0  H  0޽h ? ̙33y___PPT10Y+D=' = @B + 0 0(  0x 0 c $C `}   r 0 S HD `  X 0 C 0A100_1736[1] PH 0 0޽h ? 33___PPT10i.Vq+D=' = @B + 0 4*(  4x 4 c $C `}   r 4 S PD P  H 4 0޽h ? 33___PPT10i.VP)׾+D=' = @B + 0 @<(  ~  s *@C `}   ~  s *D `  H  0޽h ? 33___PPT10i.V $]+D=' = @B + 0 `6(  ~  s *TC `}   x  c $D `  H  0޽h ? 33___PPT10i.Vk+D=' = @B + 0 (6(  (~ ( s *C `}   x ( c $D `  H ( 0޽h ? 33___PPT10i.~X +D=' = @B +} 0 `P$(  Pr P S C `}   r P S dD `  H P 0޽h ? h___PPT10i.]02#+D=' = @B + 0 0(PL(  Lr L S lC `}   x L c $D `   L NAAA ?D  H L 0޽h ? h___PPT10i.[`_'+D=' = @B + 0 6.,(  ,x , c $#C `}   x , c $#D @   , NAAA ?DZ H , 0޽h ? 33___PPT10i.Vh%+D=' = @B +  0 pT6(  T~ T s *1C `}   x T c $t2D `  H T 0޽h ? 33___PPT10i.VY)+D=' = @B + 0 PT{(  Tx T c $PԤC `}   r T S PD `  I T 0@PPE  There is evidence for lack of benefit in the 7 month old 31 weeker No evidence for benefit in cystic fibrosis patient but is reasonable to consider 2<RH T 0޽h ? 33___PPT10i.V @+D=' = @B + 0 `X*(  Xx X c $JC `}   r X S LD `  H X 0޽h ? 33___PPT10i.VT+D=' = @B +0 0(`(  `X ` C \   ( ` S \ 0   zRSV is a single-stranded, negative-sense RNA virus and a member of the Paramyxoviridae family. Two subtypes, A and B, are simultaneously present in most outbreaks, with A subtypes typically causing more severe disease Several distinct genotypes within these subtypes predominate within a community; the dominant strains shift yearly, perhaps accounting for frequent reinfections,G H ` 0޽h ? 3380___PPT10.VҠ>0 dN(  dX d C \    d S \ 0   PTransmission Transmission of RSV is primarily by inoculation of nasopharyngeal or ocular mucous membranes after contact with virus-containing secretions or fomites Direct contact is the most common route of transmission, but large aerosol droplets also have been implicated RSV can survive for several hours on hands and fomites [Hand washing and contact precautions are therefore important measures to prevent nosocomial spread. The period of viral shedding usually is three to eight days, but it may last up to four weeks in young infants. The incubation period ranges from two to eight days W K  P S H d 0޽h ? 3380___PPT10.Vu0 *"h(  hX h C \   " h S н\ 0   *Immunity Although virtually all individuals have been infected with RSV by age 3 years, previous infection with RSV does not appear to convey complete protection against reinfection, even when significant specific antibody titers are present Humoral immunity may be more important in ameliorating the severity of RSV infection than in preventing disease entirely, based upon the following observations: Individuals can be infected more than once in the same RSV season; however, subsequent infections are usually milder whether they occur in the same season or in different years Transplacentally acquired antibody against RSV does not protect infants against infection. However, infants with high antibody titers usually have milder symptoms restricted to the upper respiratory tract  > =KH h 0޽h ? 3380___PPT10.V~0 l-(  lX l C \    l S \ 0   /Pathologic findings of RSV include necrosis of epithelial cells, occasional proliferation of the bronchiolar epithelium, infiltrates of monocytes and T cells centered on bronchial and pulmonary arterioles, and neutrophils between the vascular structures and small airways This leads to airway obstruction, air trapping and increased airway resistance, and also is associated with a finding of neutrophilia in bronchoalveolar lavage b A  H l 0޽h ? 3380___PPT10.V4  0 n f t(  tX t C \   f t S X\ 0   dDose and schedule The dose of Palivizumab is 15 mg/kg IM once per month for a total of five doses. The first dose is administered before the RSV season begins (usually in November, but may vary by geographic region). Once immunoprophylaxis is initiated, all five doses should be administered, even if the infant becomes old enough that prophylaxis is no longer indicated [1,27]. As an example, an infant born at 29 weeks who is without BPD or congenital heart disease and turns 6 months old in January should still receive immunoprophylaxis in February and March. Immunoprophylaxis also should continue even if the infant experiences breakthrough infection [1]. This is because high-risk infants may be hospitalized more than once during an RSV season and more than one strain of RSV may cocirculate in a community. R3 K  M 0 +0vz0H t 0޽h ? 3380___PPT10.V`%0 H@(  d  c $\#7   4  s *\ @    Numerous studies have demonstrated that respiratory sequelae may occur following acute bronchiolitis in infancy. A literature review revealed that several groups have observed recurrent lower respiratory symptoms following RSV bronchiolitis, but the percentage of children affected diminished over time.1 Henry and colleagues2 found wheezing and/or acute lower respiratory tract disease lasting at least 2 weeks in 82% of the 55 children evaluated 2 years after hospitalization for RSV bronchiolitis. Webb et al3 reported similar symptoms in 69% of 81 children followed 3.5 years after hospitalization for acute bronchiolitis during the RSV season. Hall and coworkers4 reported that 55% and 24% of their 29 patients experienced respiratory symptoms 4 to 5 years and 6 to 8 years, respectively, following the initial infection. Although RSV bronchiolitis may not cause lifelong respiratory problems, it appears to be associated with prolonged respiratory morbidity during the developmental years. 1. Wolff D, Fiedelman W. J Pediatr Pharm Pract. 1999;4:23. 2. Henry RL et al. Arch Dis Child. 1983;58:713. 3. Webb MSC et al. Arch Dis Child. 1985;60:1064. 4. Hall CB et al. J Pediatr. 1984;105:358. Strong association between RSV LRI and asthma during childhood, but resolves by 10 years of age (causality not established). 23% had asthma at 3 years post  RSV. 30% had asthma at 7.5 years post  RSV.4q~s          \B Ab B B B B "B B "B B B  f4                   s                           %    -    *      H  0޽h ? ̙33@0 (  d  c $\#7     s *X3\ @   z Worldwide epidemics occur yearly. In United states, these epidemics occur from November through March. More than fifty percent of infants are infected by one year of age. Almost all children are infected by two years of age. Reinfection is frequent throughout life. 0 i    H  0޽h ? ̙330 B:P(  d  c $\#7   .  s *0E\ @   Based on the IMpact study, the efficacy of Synagis in reducing severe RSV infection is 39% in infants with CLD and up to 82% in premature infants without CLD. Synagis is available in fifty and one hundred mg vials. The cost of Synagis is $725 per 50 mg vial and almost $1400 per 1 mg vial. The cost of Synagis is estimated to be four thousand dollars per infant receiving monthly prophylaxis during the RSV season. Synagis has a shelf life of six hours making drug wastage nearly inevitable. NEXT SLIDE 0i t n=EjSH  0޽h ? ̙330 G?(  d  c $\5   3  s *tW\ @   1Respiratory syncytial virus is the primary cause of lower respiratory tract illness in young children. By 2 years of age, almost all children have been infected by RSV. While it generally resolves uneventfully in otherwise healthy children, high risk populations, such as premature infants may develop severe and sometimes fatal lower respiratory tract infections. RSV infection contributes annually up to one twenty six thousand, three hundred pediatric hospitalizations. Analyses of the 1993 National Inpatient Sample of the Healthcare Cost and Utilization Project estimate the annual hospitalization costs for RSV pneumonia to be between 300 and 400 million dollars in 1998 dollars. Annual mortality due to RSV in infants and children is estimated to range from two hundred to over two thousand seven hundred. R/i h1 H  0޽h ? ̙330 "(  X  C \     S dr\ 0   ZRSVIG was a polyclonal hyperimmune globulin prepared from donors with high serum titers of RSV neutralizing antibody In controlled trials RSVIG reduced RSV-associated hospitalizations among high risk infants by 41 to 63 percent However, its use was associated with increased morbidity and mortality in infants with congenital heart disease and it was never labeled for use in these infants In addition, as a blood product, RSVIG had the potential to interfere with the immune response to certain live virus vaccines (eg, measles/mumps/rubella and varicella) and to be contaminated adventitious agents. >  /H  0޽h ? 3380___PPT10.W 0 B:(  X  C \   :  S t]\ 0   lPalivizumab Palivizumab is a humanized monoclonal antibody against the RSV F glycoprotein (which is highly conserved among various isolates). It is licensed for use in selected infants and children younger than 24 months with BPD, preterm birth ( 35 weeks), or hemodynamically significant congenital heart disease Even before the discontinuation of RSVIG, palivizumab was preferred because of its ease of administration and lack of interference with immune response to MMR and varicella vaccines Another more potent RSV-neutralizing antibody, MEDI-524 or Numax, was derived from palivizumab It appears to be more effective than palivizumab in animals and is undergoing clinical evaluation @  - f    P n F & 500FQH  0޽h ? 3380___PPT10.W]/0 ?(  X  C \     S x\ 0   ATherapy for respiratory syncytial virus (RSV) infection of the lower respiratory tract is primarily supportive. Supportive care may include hospitalization and fluid and respiratory support. We suggest a trial (single administration) of therapy with a beta-agonist (albuterol or epinephrine) if bronchospasm is clinically apparent Therapy should be discontinued in patients who fail to demonstrate rapid improvement. We recommend not using corticosteroids in infants with RSV bronchiolitis or pneumonia However, corticosteroids may be beneficial in the management of bronchospasm in older children and adults. We recommend not using ribavirin routinely in the management of infants and children with RSV LRTI. However, ribavirin may be beneficial in infants and children at risk for severe RSV lower respiratory tract infection (LRTI). We suggest ribavirin in combination with passive immunotherapy and/or corticosteroids for immune compromised adults with severe RSV LRTI Neither intravenous immunoglobulin with a high neutralizing activity against RSV (RSVIG) nor monoclonal antibody have proven beneficial in the treatment of RSV in hospitalized infants and young children. H       N 7 M x B0 00|H  0޽h ? 3380___PPT10.W "0   P0 (  ^  S \      c $ \ 0   & Risk factors Patients at risk for lower respiratory tract disease include: Infants younger than 6 months of age [14], particularly those who are born during the first half of the RSV season and those attending daycare [15] Infants and children with underlying lung disease such as chronic lung disease (bronchopulmonary dysplasia) [14,16] Infants born before 35 weeks gestation [14,16] Infants and children with congenital heart disease [14,17] Immunocompromised patients (eg, severe combined immunodeficiency, leukemia, or bone marrow or lung transplant) [17-20] Patients of any age group with significant asthma Residence at altitude >2500 m [21] Institutionalized elderly [9] Elderly patients with chronic pulmonary disease or functional disability ghp+7sUL  shS +7 RUL0su00OT0003800H  0޽h ? 3380___PPT10.%Y)#0  p(  ^  S \     c $h\ 0   <Adverse events Rare cases of severe hypersensitivity reactions (<1 per 100,000 recipients) have been described after an initial dose as well as after reexposure. In two studies evaluating the safety of palivizumab during two consecutive seasons, no serious adverse events were noted. Only 1 of 118 children had a significant increase in antipalivizumab antibody titer and the antibody response declined with continued dosing. The development of RSV resistant to palivizumab is another potential adverse effect, although in a study of 458 palivizumab-treated infants no escape mutants were detected. Palivizumab does not interfere with routine childhood immunizations. @  ; | * |n A 1 ;00XdH  0޽h ? 3380___PPT10.YptK%0 NKFK,J(  ,^ , S \   @J , c $8\ 0   IEPalivizumab or RSV-IGIV prophylaxis should be considered for infants and children younger than 2 years with CLD who have required medical therapy (supplemental oxygen, bronchodilator, diuretic or corticosteroid therapy) for CLD within 6 months before the anticipated start of the RSV season. Palivizumab is preferred over RSV-IGIV for most high-risk children because of its ease of administration, safety, and effectiveness. (Evidence grade I*.) Patients with more severe CLD may benefit from prophylaxis during a second RSV season if they continue to require medical therapy for pulmonary or cardiac dysfunction. Individual patients may benefit from decisions made in consultation with neonatologists, pediatric intensivists, pulmonologists, or infectious disease specialists. There are limited data regarding the effectiveness of palivizumab during the second year of life, although children with CLD or CHD who require ongoing medical therapy may experience severe RSV infections. Infants born at 32 weeks gestation or earlier may benefit from RSV prophylaxis even if they do not have CLD. For these infants, major risk factors to consider include their gestational age and chronologic age at the start of the RSV season. (Evidence grade I.) {bl}Infants born at 28 weeks gestation or earlier may benefit from prophylaxis during their first RSV season whenever that occurs during the first 12 months of life. Infants born at 29 to 32 weeks gestation may benefit most from prophylaxis up to 6 months of age. For the purpose of this recommendation, 32 weeks gestation refers to an infant born on or before the 32nd week of gestation (ie, 32 weeks, 0 days). Once a child qualifies for initiation of prophylaxis at the start of the RSV season, administration should continue throughout the season and not stop at the point an infant reaches either 6 or 12 months of age. Although palivizumab and RSV-IGIV have been shown to decrease the likelihood of hospitalization for infants born between 32 and 35 weeks of gestation (ie, between 32 weeks, 1 day, and 35 weeks, 0 days) (Evidence grade I), the cost of administering prophylaxis to this large group of infants must be considered carefully. Most experts recommend that prophylaxis be reserved for infants in this group who are at greatest risk of severe infection and who are younger than 6 months at the start of the RSV season. Epidemiologic data suggest that RSV infection is more likely to lead to hospitalization for these infants when the following risk factors are present: child care attendance, school-aged siblings, exposure to environmental air pollutants, congenital abnormalities of the airways, or severe neuromuscular disease. However, no single risk factor causes a very large increase in the rate of hospitalization, and the risk is additive as the number of risk factors for an individual infant increases. Therefore, prophylaxis should be considered for infants between 32 and 35 weeks gestation only if 2 or more of these risk factors are present. Exposure to tobacco smoke is a risk factor that can be controlled by the family of an infant at increased risk of RSV disease, and tobacco smoke control measures will be far less costly than palivizumab prophylaxis. High-risk infants never should be exposed to tobacco smoke. High-risk infants should be kept away from crowds and from situations where exposure to infected individuals cannot be controlled. Participation in child care should be restricted during the RSV season for high-risk infants whenever feasible. Parents should be instructed on the importance of careful hand hygiene. All high-risk infants and their contacts should be immunized against influenza beginning at 6 months of age. Prophylaxis against RSV should be initiated just before the onset of the RSV season and terminated at the end of the RSV season. In most seasons and in most regions of the Northern Hemisphere, the first dose of palivizumab should be administered at the beginning of November, and the last dose should be administered at the beginning of March, which will provide protection into April.5 (Evidence grade III.) To understand the epidemiology of RSV in their area, physicians should consult with local health departments or diagnostic virology laboratories or the Centers for Disease Control and Prevention if such information is not available locally. Decisions about the specific duration of prophylaxis should be individualized according to the duration of the RSV season. Pediatricians may wish to use RSV hospitalization data from their own region to assist in the decision-making process. Children who are 24 months or younger with hemodynamically significant cyanotic and acyanotic CHD will benefit from 5 monthly intramuscular injections of palivizumab (15 mg/kg). (Evidence grade I.) Decisions regarding prophylaxis with palivizumab in children with CHD should be made on the basis of the degree of physiologic cardiovascular compromise. Infants younger than 12 months with CHD who are most likely to benefit from immunoprophylaxis include: i. infants who are receiving medication to control congestive heart failure; ii. infants with moderate to severe pulmonary hypertension; and iii. infants with cyanotic heart disease. Because a mean decrease in palivizumab serum concentration of 58% was observed after surgical procedures that use cardiopulmonary bypass, for children who still require prophylaxis, a postoperative dose of palivizumab (15 mg/kg) should be considered as soon as the patient is medically stable. The following groups of infants are not at increased risk from RSV and generally should not receive immunoprophylaxis: infants and children with hemodynamically insignificant heart disease (eg, secundum atrial septal defect, small ventricular septal defect, pulmonic stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta and patent ductus arteriosus) infants with lesions adequately corrected by surgery unless they continue to require medication for congestive heart failure infants with mild cardiomyopathy who are not receiving medical therapy Dates for initiation and termination of prophylaxis should be based on the same considerations as for high-risk preterm infants. Unlike palivizumab, RSV-IGIV is contraindicated in children with cyanotic CHD. Palivizumab or RSV-IGIV prophylaxis has not been evaluated in randomized trials in immunocompromised children. Although specific recommendations for immunocompromised patients cannot be made, children with severe immunodeficiencies (eg, severe combined immunodeficiency or severe acquired immunodeficiency syndrome) may benefit from prophylaxis. If these infants and children are receiving standard IGIV monthly, physicians may consider substitution of RSV-IGIV during the RSV season. (Evidence grade III.) Because RSV-IGIV and palivizumab are not effective in the treatment of RSV disease, neither is licensed for this indication. (Evidence grade I.) Limited studies suggest that some patients with cystic fibrosis may be at increased risk of RSV infection. However, there are insufficient data to determine the effectiveness of palivizumab use in this patient population. If an infant or child who is receiving immunoprophylaxis experiences a breakthrough RSV infection, prophylaxis should continue through the RSV season. (Evidence grade III.) This recommendation is based on the observation that high-risk infants may be hospitalized more than once in the same season with RSV lower respiratory tract disease and the fact that more than one RSV strain often cocirculates in a community. Physicians should arrange for drug administration within 6 hours after opening a vial, because this product does not contain a preservative. Recommendations cannot be made regarding the use of palivizumab as a means of prevention of nosocomial RSV disease. RSV is known to be transmitted in the hospital setting and to cause serious disease in high-risk infants. In high-risk hospitalized infants, the major means to prevent RSV disease is strict observance of infection control practices including the use of rapid means to identify and isolate RSV-infected infants. If an RSV outbreak is documented in a high-risk unit (eg, pediatric intensive care unit), primary emphasis should be placed on proper infection control practices, especially hand hygiene. Palivizumab does not interfere with the response to vaccines. Infants and children receiving prophylaxis with RSV-IGIV should have immunization with measles-mumps-rubella and varicella vaccines deferred for 9 months after the last dose of RSV-IGIV. The use of RSV-IGIV should not alter the primary immunization schedule for other recommended immunizations. Available data at this time do not support the need for supplemental doses of any of these routinely administered vaccines. LPP(P  '    [  }   ( = G       ? H1/' % JM   |  -00H , 0޽h ? 3380___PPT10.~X8 0 8(  8X 8 C \    8 S t)\ 0   bEfficacy and effectiveness The efficacy of palivizumab for preventing severe RSV infection in infants and children with prematurity, BPD, and congenital heart disease has been demonstrated in randomized controlled trials: In the IMpact-RSV Trial, 1502 patients with BPD and/or prematurity (<35 weeks) were randomly assigned to monthly treatment with palivizumab or placebo Palivizumab was associated with significantly fewer RSV-associated hospitalizations (4.8 versus 10.6 percent with placebo, a 55 percent reduction). In another trial, 1287 children with hemodynamically significant congenital heart disease were randomly assigned to monthly treatment with palivizumab or placebo Palivizumab was associated with fewer RSV-associated hospitalizations (5.3 versus 9.3 percent, a 45 percent reduction), fewer hospital days requiring oxygen (178 versus 658, a 73 percent reduction) and fewer total hospital days (367 versus 876, a 56 percent reduction). The mortality rates were similar in both groups (3.3 versus 4.3 percent). No deaths or adverse events were attributed to palivizumab. Post-licensure surveillance indicates the RSV-associated hospitalization rates among high risk infants who receive palivizumab are similar to or lower than the RSV-associated hospitalization rates described above Whether prevention of RSV LRTI with palivizumab affects the incidence of subsequent episodes of recurrent wheezing was evaluated in a cohort of 421 premature infants without chronic lung disease Of these, 191 received palivizumab prophylaxis and were not hospitalized for RSV and 230 did not receive palivuzumab (76 were hospitalized for RSV and 154 were not). The incidence of physician diagnosed recurrent wheezing between 19 and 43 months of age was decreased in the palivizumab group (8 versus 16 percent). This preliminary finding suggests that prevention of RSV LRTI may reduce the risk of recurrent wheezing in premature infants without chronic lung disease b   ~  {  k  - B b* >  W  | v {  G  0-800<GH 8 0޽h ? 3380___PPT10."Z+] 0 <m(  <X < C \    < S H]\ 0   oThere are multiple challenges to the development of a successful RSV vaccine. Immature immunity and possible suppression of an immune response by maternal antibody are issues in the target population of young infants. The vaccine must be protective against antigenically divergent strains. In addition, it must not potentiate disease in recipients who subsequently become infected with wild-type virus, as occurred in trials with a formalin-inactivated vaccine developed in the 1960s Live attenuated RSV vaccines are being developed and tested. Although several biologically attenuated candidate vaccines have induced an antibody response in young infants, they have been insufficiently attenuated for use in this age group Recombination technology has been used to produce an attenuated strain that was well tolerated by 1- to 2-month old infants in one report However, only 44 percent of subjects had a detectable antibody response. Subunit vaccines have been developed from RSV F and G glycoproteins. 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