Immunoprophylaxis for Prevention
of Severe RSV Bronchiolitis
Ma. Teresa C. Ambat, MD
Neonatology-TTUHSC
11/21/2008
Development of Immunoprophylaxis

1996: FDA approved the intravenous polyclonal antibody
RSV immune globulin (RSV-IVIG, Respigam)



Prepared from donors selected for high serum titers of
RSV neutralizing antibody
No longer available
1998: FDA approved palivizumab (Synagis)
 First monoclonal antibody developed into vaccine, for
use as immunoprophylaxis for children <2 yrs at risk
for severe RSV infection
Comparison of RSV-IVIG with Palivizumab
Characteristics
RSV-IVIG
(Respigam)
Palivizumab
(Synagis)
Type of immunoglobulin
Polyclonal
Monoclonal
Method of administration
IV
IM
Contraindicated in infants with
hemodynamically significant CHD
Yes
No
Protects against other viral
infections
Yes
No
Decreased AOM
Yes
No
Risk of fluid overload in BPD
Yes
No
Blood product
Yes
No
Interferes with routine childhood
immunization
Yes
No
750mg/k/dose
15mg/k/g/dose
Monthly
Monthly
5
5
Dosage
Dosing interval
# of doses / season
Clinical Practice Guideline
Diagnosis and Management of Bronchiolitis

RECOMMENDATION 8a

Clinicians may administer palivizumab prophylaxis to
selected infants and children with CLD or a history of
prematurity less than 35 weeks’ gestation or with
congenital heart disease

Recommendation: evidence level A; RCT;
preponderance of benefit over harm
Clinical Practice Guideline
Diagnosis and Management of Bronchiolitis

RECOMMENDATION 8b

When given, prophylaxis with palivizumab should be
given in 5 monthly doses, usually beginning in November
or December, at a dose of 15 mg/kg per dose
administered intramuscularly

Recommendation: evidence level C; observational
studies and expert opinion; preponderance of benefit
over cost
The 2006 Red Book Recommendations
for the use of Palivizumab
1.
Palivizumab prophylaxis should be considered for infants and
children < 24 months of age with chronic lung disease of
prematurity who have required medical therapy
(supplemental oxygen, bronchodilator or diuretic or
corticosteroid therapy) for CLD within 6 months before the
start of the RSV season.

Patients with more severe CLD who continue to require medical
therapy may benefit from prophylaxis during a second RSV season.

Data are limited regarding the effectiveness of palivizumab during
the second year of life.
The 2006 Red Book Recommendations
for the use of Palivizumab
2.
Infants born at 32 weeks of gestation or earlier may benefit
from RSV prophylaxis, even if they do not have CLD.

Major risk factors: gestational age, chronologic age at the start of the
RSV season

< 28 weeks of gestation or earlier may benefit from prophylaxis
during their first RSV season, whenever that occurs during the first
12 months of life

29 to 32 weeks of gestation may benefit most from prophylaxis up to
6 months of age

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 months or 12
months of age.
The 2006 Red Book Recommendations
for the use of Palivizumab
3.
Prophylaxis should be considered for infants between 32
and 35 weeks of gestation younger than 6 months of age at
the start of RSV season only if 2 or more of these risk
factors are present:

Child care attendance
School-aged siblings
Exposure to environmental air pollutants
Congenital abnormalities of the airways
Severe neuromuscular disease





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.
The 2006 Red Book Recommendations
for the use of Palivizumab
4.
Results from clinical trials indicate that palivizumab
trough serum concentrations 30 days after the fifth dose
will be well above the protective concentration for most
infants.

If the first dose is administered in November, 5 monthly
doses of palivizumab will provide substantially more
than 20 weeks of protective serum antibody
concentrations for most of the RSV season, even with
variation in season onset and end.
The 2006 Red Book Recommendations
for the use of Palivizumab
5.
Children who are 24 months of age or younger with
hemodynamically significant cyanotic and acyanotic
congenital heart disease will benefit from palivizumab
prophylaxis.

Children younger than 24 months of age with congenital heart
disease who are most likely to benefit from immunoprophylaxis
include:

Infants who are receiving medication to control congestive heart
failure
Infants with moderate to severe pulmonary hypertension
Infants with cyanotic heart disease


Summary of AAP Recommendations for Use
of Immunoprophylaxis in RSV Infection
1.
2.
3.





Without BPD
With BPD
Former Premature Infants
Irrespective of Prematurity
GA <28 wks, who are <12 months
old at the start of RSV season
GA >28 to <32 wks, who are < 6
months old at the start of RSV
season
GA >32 to <35 wks, who are <6
months old at the start of RSV
season and > 2 of the ffg:
Child care attendance
School-aged siblings
Congenital anomalies of the airways
Severe neuromuscular disease
Exposure to environmental air pollutants
1.
2.
<12 months old at the start of the
1st RSV season
<24 months old with persistent
signs of BPD at the start of the 2nd
RSV season
Summary of AAP Recommendations for Use
of Immunoprophylaxis in RSV Infection
1.
Infants and children with congenital heart disease

At the start of RSV season
<12 months and receiving medications to control CHF
<12 months with uncorrected or partially corrected cyanotic heart
disease who remain cyanotic
<24 months with hemodynamically significant cyanotic and
acyanotic heart disease
2.
Infants and children with pulmonary hypertension

At the start of RSV season
<12 months with moderate PPHN
<24 months with severe PPHN
Summary of AAP Recommendations for Use
of Immunoprophylaxis in RSV Infection

Dates for initiation and termination should be based on
the same considerations as for high-risk preterm infants.

For children who underwent cardiopulmonary bypass
and still require prophylaxis, a postoperative dose of
palivizumab (15mg/kg) should be considered as soon as
the patient is hemodynamically stable.
Summary of AAP Recommendations for Use
of Immunoprophylaxis in RSV Infection
3.
Infants and children not considered at risk for severe
RSV (immunoprophylax is not indicated)

Infants with non-hemodynamically significant heart disease: ASD
Small VSD, Pulmonic stenosis, mild coarctation, PDA

Infants with corrected cardiac lesions without cyanosis or CHF

Infants with mild cardiomyopathy who are not receiving medical
therapy
Additional AAP Remarks

Once a child qualifies for immunoprophylaxis, administration should
continue for the remainder of the RSV season even if the child no
longer meets the clinical criteria or age requirement prior to
completion of the RSV season.

Even if a child develops RSV during immunoprophylaxis, he or she
should complete the drug course.

Neither RSV-IVIG nor Palivizumab is indicated or licensed for the
treatment of RSV infection.

RSV prophylaxis should begin before the onset of the RSV season
(November) and terminate at the end of the RSV season (March),
allowing for 6 months of protection.
Additional AAP Remarks

All high-risk infants and their contacts should be immunized
against influenza beginning at age 6 months.

There is insufficient information regarding the
immunoprophylaxis of infants with CF, SCID, AIDS. However,
they may benefit from prophylaxis.

There are no recommendations regarding the administration of
palivizumab as a means of preventing nosocomial RSV
infection.
Additional AAP Remarks

High-risk infants should never be exposed to tobacco smoke.

Existing data are conflicting regarding the specific protective
effect of breastfeeding against RSV infection.

High-risk infants should be kept away from crowds and from
situations in which exposure to infected individuals cannot be
controlled.

Participation in group 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.
Controversies in RSV Immunoprophylaxis

Primary benefit of RSV immunoprophylaxis is decreased rate
of RSV-related hospitalizations.

No significant decrease in rate of mortality attributable to RSV
infection in infants who received prophylaxis.

Most of the economic analyses fail to demonstrate overall
savings in health care dollars because of the high cost if all atrisk children were to receive prophylaxis.

Giving immunoprophylaxis to all infants at high risk is not cost
effective.
References
1.
2006 Redbook
2.
Clinical Practice Guideline: Diagnosis and Management of
Bronchiolitis. Endorsed by the American Academy of Family
Physicians, the American College of Chest Physicians, and
the American Thoracic Society.
3.
Brodsky D, Quellette M. Primary Care of the Premature
Infant. 2008.