Annual Deaths From Acute Respiratory Infections in Under Fives*

1
Annual Deaths From Acute Respiratory Infections
in Under Fives
3.76 Million Deaths Totally
WHO Estimates
2
RSV Global Importance

• Directly or indirectly accounts for 600,000 to
  1,000,000 deaths under 5 years of age annually
• Most important pathogen after S. pneumoniae

Simoes EAF. Infect Med 1999 16Supplement C
24-30.
3
Seasonal Epidemics of RSV
From Shay, Holman, Newman, Liu, Stout and
Anderson (1999) J Am Med Assoc 2821440-46
4
Top Causes of Infant Hospitalization
Based on National Hospital Discharge Survey,
1997-1999
RSV Bronchiolitis
Bronchiolitis (cause unspecified)
Pneumonia(cause unspecified)
Jaundice
Dehydration
Leader S, Kohlhase K. Pediatr Infect Dis J.
200221629-32
5
Respiratory syncycial virus (RSV) General
Features

• Single-stranded, nonsegmentedRNA virus in the
  paramyxoviridae family
• Attachment (G) proteins assist with viral
  adherence to the host cells
• Fusion (F) proteins aid with viral penetration

RSV diagram by Dr J Randhawa available at
http//www.bio.warwick.ac.uk/easton/
6
RSV Subtypes

• There are two subtypes of RSV - A B
• There are two glycoproteins targets for
  neutralizing antibodies G-binds to a
  specific cellular receptor F-fusion of the
  virus to the cell

7
Inflammatory mediators, chemokines and cells in
epithelial infection
Neutrophils activation,chemotaxis
IL-8, Groa
GM-CSF, Eotaxin, RANTES, MIP-1a
Eosinophils survival, chemotaxis
IL-1b, MIP-1a, MCP-1, TNFa
Macrophages
virus
NK cells activation
IFNa / b, MIP-1a
T lymphocytes activation, chemotaxis
RANTES, IL-6 MCP-1 (Th2)
MHC I, ICAM-1,VCAM-1 IFNa / b
8
(No Transcript)
9
Normal bronchiole
16-fold
Inflamed bronchiole
10
Spectrum of RSV infections

• By age 2-3 all children have antibodies to RSV
• Subclinical infection
• Upper respiratory tract infection
• Lower respiratory tract infection
• Bronchiolitis
• Pneumonia

11
Spectrum of RSV infections

• 12 -40 of infants get symptoms of lower
  respiratory tract infection
• 5 get more severe bronchiolitic symptoms
• 1-2 require hospitalization2

1. Holberg CJ, Wright et al. Risk factors for
respiratory syncytial virus-associated lower
respiratory ilnesses in the first year of life.
Am J Epidemiol 19911331135-51. 2. Ruuskanen O,
Ogra P. Current problemsin Pediatrics. Chicago
Year Book. Medical
Publishers. February 1993.
12
(No Transcript)
13
Risk Factors for Severe RSV Bronchiolitis 1

• Host factors
• Extremes of age lt 6 weeks, geriatric .
• Children with premature birth lt 35W .
• Chronic illness - Broncho-Pulmonary Dysplasia
  (BPD).- Chronic Lung Disease (CLD) . -
  Congenital Heart Disease (CHD).- Immune
  deficiency/Immunosuppression.

14
Risk Factors for Severe RSV Infection - 2

• Environmental factors
• Poverty.
• Crowding (day care).
• Passive smoker.
• Malnutrition.

15
Abreu e Silva et al sleep apnea in bronchiolitis
AJDC, 198257467
Apnea and bronchiolitis

• Apnea occurs in 18-20 of hospitalized infants
  with bronchiolitis, particularly if
• lt 32 weeks gestation
• lt 44 weeks post conception
• if neonatal apnea
• Apnea may occur early, even at presentation. It
  is usually non-obstructive, centrally mediated,
  usually while asleep. The apnea lasts for a few
  days about 10 may need to be intubated.

16
Non-respiratory manifestations

• Non-respiratory manifestations
• otitis media (86) (Andrade, Peds1998)
• myocarditis
• supraventricular tachycardia
• ventricular dysrrhythmias (Thomas
  CCM 1997)
• SIADH (Rivers Arch Dis Chil, 1981)
• encephalitis

17
Is there a link between RSV bronchiolitis and
reactive airway disease?
18
Follow-up studies with control groups after RSV
bronchiolitis and unspecified bronchiolitis

• Higher prevalence of bronchial obstructive
  symptoms in children after bronchiolitis compared
  to controls
• In some studies lower FEV1 and FEF25-75 many
  years after bronchiolitis
• In some studies increased airway
  hyperresponsiveness many years after
  bronchiolitis
• Family history atopy/asthma the same

19
Questions

• Does RSV bronchiolitis per se increase the risk
  of asthma and bronchial symptoms?
• or
• Do children with some inherent risk factor(s)
  develop bronchiolitis and subsequent wheezing?
• Is there a difference in the risk for subsequent
  bronchial obstructive symptoms between children
  with RSV infection which requires hospitalization
  and milder infections?

20
Sigurs N, Bjarnason R et al 1995 and 2000.
Prospectively followed up to age 7

• 47 infants hospitalized with RSV bronchiolitis
  winter season 1989-90
• mean age 116 days, 91 lt6 months, the eldest 10
  months
• first episode of bronchial obstructive symptoms
• 93 controls recruited during infancy, matched for
  age, sex and place of living

Ref N.Sigurs, R. Bjarnason, F. Sigurbergsson, B.
Kjellman. Respiratory Syncytial Virus
Bronchiolitis in Infancy Is an Important Risk
Factor for Asthma and Allergy at Age 7, American
Journal of Respiratory and Critical Care Medicine
VOL 161 2000 1501-1507.
21
Combination of RSV bronchiolitis and family
history of asthma and development of asthma at
age 7, Sigurs et al 2000
Asthma

n.s.
n.s.
plt0.05 plt0.01 plt0.001



Family history of asthma No No
Yes Yes RSV- bronchiolitis
No Yes No Yes Asthma
/ all 3/66
6/26 0/27
8/21
22
Some possible predisposing factors for
bronchiolitis and/or post-bronchiolitic symptoms

• Diminished lung function before RSV 1, 2, 3
• Family history atopy/asthma 4, 5
• Smoking in family 4, 5
• Length of breast feeding 4, 5
• .

1. Martinez FD, Wright AL et al. Asthma and
wheezing in the first six years of life. N Engl
J Med 1995.332133-8. 2. Young S, OKeefe, AJ,
LandauLI. Lung function, airway responsiveness
and respiratory symptoms before and after
bronchiolitis. Arch Dis Child 1995.7216-24. 3.
Palmer LJ, Rye P et al. Airway responsiveness in
early childhood predicts asthma, lung function
and respiratory symptoms by school age. Am J
Respir Crit Care Med 2001.16337-42. 4. Noble V,
Murray M et al. 1997. Respiratory status and
allergy nine to 10 years after acute
bronchiolitis. Arch Dis Child. 76315-19. 5.
Sigurs N, Bjarnason R et al. Respiratory
syncytial virus bronchiolitis in infancy is an
important risk factor for asthma and allergy at
age 7. Am J Respir Crit Care Med.
2000.1611501-7.
23
Multivariate test of risk factors for allergic
sensitization in all 140 children
Ref N.Sigurs, R. Bjarnason, F. Sigurbergsson, B.
Kjellman. Respiratory Syncytial Virus
Bronchiolitis in Infancy Is an Important Risk
Factor for Asthma and Allergy at Age 7, American
Journal of Respiratory and Critical Care Medicine
VOL 161 2000 1501-1507.
24
(No Transcript)
25
RSV Bronchiolitis --Prevention

• General Measures
• Active Immunity Vaccine
• Passive Immunity Polyclonal antibody(IVIG)
• Monoclonal
  antibody( IMI )
• 
  

26
Prevention

• RSV is transmitted via secretions. Prevention
  includes
• hand washing
• gowns and gloves (Hall, Peds1978)
• cohorting patients
• reducing visits by children
• But asymptomatic adults may transmit infection.
  And day care centers are common sites of
  epidemics.

27
RSV-IGIV Conclusions

• RSV LRI
• RSV hospitalization
• RSV LRI hospitalization
• Acute otitis media
• RSV hospitalization lt 6 months

PREMIES
CARDIAC
28
WHAT IS ABBOSYNAGIS ?

• Generic name is palivizumab (pal ee VEE zoo mab).
• It is a humanized monoclonal antibody (IgG1)
  produced by recombinant DNA technology to bind
  the F protein and neutralize RSV.
• The mean half-life of ABBOSYNAGIS is 20 days.
  Abbosynagis should be given by IM injection
  every 30 days.
• The serum mean trough levels of ABBOSYNAGIS
  remain above an ideal therapeutic threshold of 40
  µg/mL with repeated monthly injections.

29
Humanization of a Murine Mab
Mouse Mab
Human Frame
Humanized Mab
30
IMPACT RSV

• Randomized, double-bind, placebo-controlled
• 21 randomization
• Multicenter
• US, Canada, UK
• Sample Size
• 1281(13.5 attack rate, 41 reduction)
• 1502 enrolled
• Intent-to-treat
• Analysis of all patients as randomized

31
IMpact Hospitalization Rates
(The IMpact-RSV Study Group. Pediatrics.
1998102(3)531-537.)
32
RSV prophylaxis (Combined Analysis)Infants with
BPD / CLD lt 2 years (N3,675) Mean RSV
hospitalization rates showing 95 CI
21.0
18.4
15.7
RSV Hospitalization
Rate
6.5
5.6
4.8
Not Prophylaxed
SYNAGIS
(N811 5 studies)
(N2864 7 studies)
33
Conclusions RSV Prevention

• Active prevention for RSV is problematic and no
  current vaccines are available or will be in the
  foreseeable future
• Passive prophylaxis with Palivizumab is currently
  the only option for RSV prevention in High risk
  patients

34
(No Transcript)
35
RSV Epidemiology, Populations at Risk, and
Interventions
36
Distinct Disease Syndromes Associated with RSV
Infection

• Bronchiolitis in infants
• Sudden infant death syndrome (SIDS)/apnea
• Post-infection wheezing/childhood asthma
• Severe disease in the institutionalized elderly
  leading to excess mortality and exacerbation of
  underlying disease conditions
• Giant cell pneumonia in persons with deficient
  T-cell immunity
• Vaccine-enhanced disease

Hull J, et al. Thorax. 2000551023-7 Kneyber
MC, et al. Eur J Pediatr. 1998157331-5
Lindgren C. Acta Paediatr. 199382(Suppl)38967-9
Martinez FD. Pediatr Infect Dis J. 200322(2
Suppl)S76-82 Openshaw PJ, et al. Vaccine
200120(Suppl1)S27-31
37
The Burden of RSV Disease

• RSV is the leading cause of infant
  hospitalization and a leading viral cause of
  death in infants
• More than 120,000 hospitalizations annually in
  the US.
• Infects up to 70-80 of children lt2 years each
  winter
• Of those infected, 30 will have prolonged
  wheezing
• Mortality rate for those hospitalized is lt1 in
  healthy children but 3.5 in those with
  high-risk conditions (CLD, CHD, etc.)

Leader S, Kohlhase K. PIDJ. 2002 21629
Thompson WT, et al. JAMA. 2003289179-86Shay
DK, et al. JAMA. 1999 2821440-9 Glezen WP, et
al. Am J Dis Child. 1986 140543 Welliver RC.
Semin Perinatol. 1998 2287 Navas L, et al. J
Pediatr. 1992121 348-54 LaVia WV, et al. J
Pediatr. 1992 121 (4) 503-10
38
RSV Re-infection

• Studies report that between 6 and 83 of
  children followed longitudinally have been
  re-infected each year.
• Antibody response is not sufficient to prevent
  subsequent RSV reinfection.
• RSV-infected lymphocytes and macrophages may
  suppress secondary immune responses.

Feigin RD, Cherry JD, (Eds.). Textbook of
Pediatric Infectious Diseases, 4th Ed. 1998.
185.2095 Hall CB, et al. Journal of Infectious
Diseases. 163,no.4(1991)693-8 Openshaw, P.J.M.
Respiratory Research 3, Suppl 1. (2002)S15
39
Recent Trends in RSV HospitalizationsIn the US

• Up to 126,300 annual hospitalizations among U.S.
  infants for bronchiolitis or pneumonia may be
  attributable to RSV infection.
• Annual mortality due to RSV in infants and
  children is estimated to range from 200 to over
  2,700.
• Bronchiolitis hospitalizations 1980-1996
• 1.65 million hospitalizations
• 7 million inpatient days
• 57 were in children lt6 mo
• 81 were in children lt1 year
• 239 increase in bronchiolitis hospitalizations
  in children less than six months of age

Shay DK, et al. J Infect Dis. 200118316-22
Institute of Medicine. In New Vaccine
Development Establishing Priorities. Vol I.
Wash DC Nat Aca Press 1986 397-409 Shay DK, et
al. JAMA. 19992821440-9
40
The RSV-Asthma Link

• Several prospective studies have shown that RSV
  bronchiolitis is associated with recurrent
  wheezing during subsequent years.
• Recurrent wheezing tends to diminish by early
  adolescence (age 13)
• Conclusion RSV appears to be linked to
  recurrent childhood wheezing through early
  adolescence

Sigurs N, et al. Am J Crit Care Med.
20001611501-7Taussig LM, et al. Am J
Epidemiol. 19891291219-31Stein RT, et al. The
Lancet. 1999354541-5
41
Children at Highest Risk for RSV

• Altered airway anatomy
• Absence of maternal antibody

Premature birth

• Bronchial hyper-responsiveness
• Reduced lung capacity

Chronic Lung Disease

• Pulmonary vascular hyper-responsiveness
• Pulmonary hypertension
• Increased pulmonary blood flow

Congenital Heart disease
Neuromuscular disease

• Decreased respiratory muscle strength and
  endurance

Immune deficiency

• Decreased host defenses
• Impaired capacity to eliminate virus

Adapted from a presentation by L Weisman, MD 1st
International Congress RSV, 2002
42
Problems in Premature Infants

• Respiratory Airway alteration, respiratory
  distress/failure, apnea, air leaks, CLD/BPD
• Cardiovascular Patent ductus arteriosus
• CNS Intraventricular hemorrhage, periventricular
  leukomalacia, seizures
• Renal Electrolyte imbalance, acid-base
  disturbances, renal failure
• Ophthalmologic Retinopathy of prematurity,
  strabismus, myopia
• Gastrointestinal-nutritional Feeding
  intolerance, necrotizing enterocolitis, inguinal
  hernias, failure to thrive
• Immunologic Poor defense to infection

43
Prematurity Interrupts Lung development
Premature
Term
Pseudoglandular Period (7 to 16 weeks GA)
Saccular Period (26 to 36 weeks GA)
Alveolar Period (36 to 41 weeks GA)
Canalicular Period (16 to 26 weeks GA)

• The lungs of premature infants are underdeveloped
  at birth
• Although alveoli are present in some infants as
  early as 32 weeks GA, they are not uniformly
  present until 36 weeks GA

Pictures are artistic renditions of lung
development and are designed to emphasize
terminal acinus development not the entire
conducting airway system Behrman Nelson Textbook
of Pediatrics, 16th ed., 2000. Langston C, et al.
Am Rev Respir Dis. 1984129607-13
44
Prematurity Alters Airway Anatomy

• Prematurity leads to altered airway development,
  even in the absence of clinical respiratory
  disease
• Premature exposure to the extrauterine
  environment can alter airways, even without
  mechanical ventilation or oxygen use
• Altered development is evidenced by
• ? diameters of major airways ? obstruction
• ? bronchial muscle ? airway hyper-reactivity
• ? number of goblet cells ? mucus production
  plugging

Hoo A-F, et al. J Pediatrc. 2002141652-8
Mansell AL, et al. J Pediatrc. 1987110111-5 Hja
lmarson O, et al. Am J Resp Crit Care Med.
200216583-7 Hislop AA, et al. Am Rev Resp Dis.
19891401717-26
45
Prematurity Alters Airways
Hoo A-F, et al. J Pediatrc. 2002141652-8
Hislop AA, et al. Am Rev Resp Dis.
19891401717-26 Mansell AL, et al. J Pediatrc.
1987110111-5
46
Prematurity Significantly reduced lung function

• Seemingly healthy premature infants (lt36 wk GA)
  have persistent abnormal lung function
• 6-10 weeks after birth significant obstruction
  (? FEF) in otherwise healthy 30-34 wk GA infants
  (plt0.001)
• At age 1 significant peripheral obstruction (?
  VmaxFRC) in otherwise healthy 29-36 wk GA infants
  (plt0.05)
• At age 6-7 significant obstruction (13 ? FEV1)
  in moderately low birth weight infants (plt0.01)
• The Point Premature infants have less pulmonary
  reserve and are more susceptible to severe
  respiratory disease

Friedrich L, et al. Am J Resp Crit Care Med.
2003167(7 Suppl)A593 Hoo A-F, et al. J
Pediatrc. 2002141652-8 Mansell AL, et al. J
Pediatrc. 1987110111-5
47
Prematurely Decreased Maternal Antibody
Transfer

• Antibody transfer occurs during the third
  trimester (after 28 weeks)
• Antibody levels at birth are proportional to
  gestational age
• Antibody levels are also influenced by
  birthweight, independent of gestational age

Yeung CY, Hobbs JR. Lancet. 196875531167-70
Okoko JB, et al. Trop Med Int Health.
20016529-34
48
Serum Antibody (IgG) Levels at Birth Premature
Term infants
Adapted from data and formulas as published by
Yeung CY, Hobbs JR. Lancet. 196875531167-70
49
Summary Risk of RSV in Premature Infants

• Hospitalization rates demonstrate that premature
  infants up to 36 wks GA are potentially high risk
  for severe RSV
• Premature infants, even those without a history
  of ventilation or oxygen use, are high risk due
  to
• Altered airway anatomy-significant obstruction
  seen throughout early childhood
• Immature immunity-impaired cellular and humoral
  immunity

50
RSV and Congenital Heart Disease

• RSV is associated with increased morbidity and
  mortality. Statistics among children hospitalized
  with RSV
• 25-33 admission to PICU
• 11-24 mechanical ventilation
• 3.4 fatality rate
• CHD patients with associated pulmonary
  hypertension are at highest risk for
  complications.
• Elective cardiac surgery should not be performed
  in an infant who has not fully recovered from RSV
  infection.

Navas L, et al. J Pediatr. 1992121348-54
Altman CA, et al. Pediatr Cardiol.
200021433-8 Moler FW, et al. Crit Care Med.
1992201406-13 MacDonald NE, et al. N Engl J
Med. 1982307397-400 Khongphatthanayothin A,
et al. Crit Care Med. 1999271974-81
51
Risk Factors in CHD Patients

• Compromised cardiorespiratory status at baseline
• Altered pulmonary mechanics may contribute to
  disease severity
• Pulmonary hypertension may exacerbate the adverse
  effects of respiratory disease
• Inability to properly compensate for intercurrent
  disease

52
Other Risk Factors for Severe RSV

• Prematurity, CHD, CLD, and age at season onset
  are well established risk factors
• Several other risk factors have been documented.

Susceptibility Factors
Low Birth Weight Exposure to tobacco smoke and other air pollutants Multiple birth Family history of asthma Minimal breast feeding






Exposure Factors
Daycare Siblings and crowded living conditions Multiple birth Maternal education level






Holman R, Shay D, et al. Pediatr Infect Dis J.
200322483-9 Boyce TG, et al. J Pediatr.
2000137865-70 Carbonell-Estrany X, et al. Ped
Infect Dis J. 200120874-9 Carbonell-Estrany
X, Quero J, Bustos G, et al. Pediatr Infect Dis
J. 200019(7)592-7 Eriksson M, et al. Acta
Paediatr. 200291593-98 McConnochie KM,
Roghmann KJ. Am J Dis Child. 1986140 806-12
Holberg CJ, et al. Am. J. Epidemiol.
19911331135-51 Meissner HC, et al. Pediatr
Infect Dis J. 199918223
53
CDC Bronchiolitis Mortality Study LBW as a Risk
Factor

• Multiple cause-of-death and linked birth/infant
  death data for 1996-1998 were used to examine
  bronchiolitis-associated infant deaths. Deaths
  were compared to surviving infants.
• Birthweight lt2500 g was a key risk factor for
  bronchiolitis-associated death, even when taking
  into account other factors (including GA)

Birthweight
Odds Ratio (95 CI)
lt1500 g
25.5 (14.6, 44.6)
1500-2499 g
4.6 (3.2, 6.8)
?2500 g
Referent
Holman R, Shay D, et al. Pediatr Infect Dis J,
2003 22 483-9
54
Therapeutic Options for RSV Bronchiolitis

• Prevention
• Limit exposure
• Passive immunoprophylaxisAbbosynagis
  (palivizumab)
• Supportive care
• Overcoming airway obstruction and inflammation
• Antiviral agents

55
RSV Prophylaxis Reserved for the Highest Risk
Children

• RSV immunoprophylaxis is the only available safe
  and effective method for preventing severe RSV
  disease
• Prophylaxis is reserved for high risk infants and
  children
• Premature infants lt36 wks GA are at a
  significantly elevated risk of severe RSV disease
• Children with chronic lung disease, congenital
  heart disease, immunodeficiencies, and other
  high-risk conditions

The IMpact-RSV Study Group. Pediatrics.
1998102(3)531-7 Boyce TG, et.al. J. Pediatr.
2000137865-70Imaizumi S, et al. Abstract
2311APS/SPR/APA-2001Law BJ, et al. CAAC 1998
(abstract MN-9)Meissner HC, et al. Pediatr
Infect Dis J. 199918223
56
RSV Prophylaxis Reserved for the Highest-Risk
Children

• All high-risk groups have significant need for
  ICU care and mechanical ventilation when
  hospitalized

High-Risk Group ICU Admission Ventilation
Premature 28-34 7-22
CLD 32 17
CHD 25-33 11-24
Boyce TG, et al., J. Pediatr. 2000 137865-70
Law BJ, et al., Paediatr. Child Health
19983402-4 Imaizumi S, Agarwal, S., and
Pereira, G.R. APS/SPR/APA 2001 convention.
4-28-2001. Abstract. Navas L, et al. J
Pediatr. 1992 121 348-54 Altman CA et al.
Pediatr Cardiol. 2000 21 433-8. Moler FW et
al. Crit Care Med.
57
Abbosynagis (Palivizumab)Mechanism of Action

• Palivizumab is a monoclonal antibody that binds
  the F protein of RSV
• Produced using recombinant DNA technology
• Palivizumab blocks the fusion of infected cells
• Reduces viral activity and cell-to-cell
  transmission of the virus

58
IMPACT-RSV TRIAL RSV Hospitalization Rates by
Subgroup
Placebo 1996-1997 IMpact-RSV trial (n500)
Abbosynagis (palivizumab) 1996-1997 IMpact-RSV
trial (n1,002)
12
10
11.0
10.6
9.8
8
6
5.8
4.8
4
2
2.0
0
All patients
All lt 32 weeks GA
All 32-35 weeks GA
55 47
80
Reduction in hospitalization rate ()
The IMpact-RSV Study Group. Pediatrics.
1998102(3)531-7
59
Palivizumab CHD Study RSV Hospitalization Rates
Reduction in hospitalization rate ()
Pediatric Cardiology. 2002 23(6) 664, Data on
file, MedImmune, Inc
60
SYNAGIS (PALIVIZUMAB) OUTCOMES REGISTRY
2000-2002 RSV Hospitalization Outcomes
The IMpact-RSV Study Group. Pediatrics. 1998
102(3) 531-7 Palivizumab Outcomes Study Group,
Pediatric Pulm. 200335484-9 Hudak et al. J
Perinatol. 2002 22619, abstract P32 Data on
file, MedImmune Inc
61
American Academy of Pediatric Vs.
MOHGuidlines1,2

•  
•  
•  
•  
•  
• 1.The Israeli MOH guidlines for RSV prophylaxis
  (Nov 05)
• 2. Revised indications for the use of
  palivizumab and resperatory synsycial virus
  immune globulin intravenous for the prevention of
  respiratory syncycial virus infections. AAP
  policy statement Pediatrics Vol 112 1442-1446,
  December 2003.
•  
•  
•  
•  

62
Synagis (Palivizumab)Timing Duration of
Prophylaxis

• RSV prophylaxis should be initiated prior to the
  onset of RSV season and terminated at the end of
  the RSV season.
• In Israel the RSV season lasts from November to
  March.
• Abbosynagis (palivizumab) does not interfere
  with vaccine administration.
• High-risk patients, including those who develop
  an RSV infection, should receive monthly doses of
  Abbosynagis throughout the RSV season.
  Acquisition of RSV is not protective against
  subsequent exposures.

Synagis (palivizumab) Package Insert
63
Synagis (Palivizumab) Package Insert (PI)

• INDICATIONS
• Abbosynagis is indicated for the prevention of
  serious LRT disease caused by RSV in pediatric
  patients at high risk of RSV disease and
  Haemodynamically Significant Congenital Heart
  Disease (CHD) in Children Less Than 2 Years of
  age.
• Safety and efficacy were established in infants
  with BPD and infants with a history of
  prematurity (35 weeks gestational age).

64
Synagis (Palivizumab) Package Insert (PI)

• Precautions
• Abbosynagis (palivizumab) is for IM use
  only and should be given with caution to patients
  with thrombocytopenia or any coagulation
  disorder.
• Adverse Events
• In clinical trials, the most common adverse
  events potentially related to Abbosynagis were
  fever, injection site reactions and nervousness.

65
Synagis (Palivizumab) Package Insert (PI)

• Contraindications
• Should not be used in pediatric patients
  with a history of a severe prior reaction to
  Abbosynagis (palivizumab) or other components of
  this product.
• Warnings
• Very rare cases of anaphylaxis (lt1 case per
  100,000 patients) have been reported following
  re-exposure to Abboynagis (palivizumab). Rare
  severe acute hypersensitivity reactions have also
  been reported on initial exposure or re-exposure
  to palivizumab.

66
Importance of Compliance

• Compliance is key for ensuring good outcomes
• In a study of 10,390 infants receiving
  Abbosynagis, non-compliant patients had 2.2x
  increase in hospitalization risk (95 Cl
  1.4-3.5, plt0.001) 3.1 vs. 1.4 hospitalization
  rate
• Compliance was defined as having on average 35
  days between doses

Berger J, et al. APA/SPR/APS 2003. Abstract
2646
67
Summary

• RSV is a significant viral pathogen, producing
  annual epidemics
• RSV bronchiolitis is a major threat to the health
  of all infants and can lead to hospitalization
  and death
• The threat of RSV is greatest in high-risk
  groups, such as infants born prematurely and
  children with CLD or CHD
• Treatment options are limited and thus RSV
  prophylaxis is essential for minimizing RSVs
  impact on high-risk children

68
Structure of RSV
69
(No Transcript)
70
(No Transcript)
71
(No Transcript)
72
(No Transcript)
73
(No Transcript)
74
(No Transcript)
75
Bart N Lambrecht Clin Exp Allergy 31(2)206-218
(2001)
76
(No Transcript)
77
(No Transcript)
78
(No Transcript)