Preventing hospitalizations for respiratory syncytial virus infection

Question 1

What percentage of all infants are hospitalized with RSV infection?

Answer 1

1-3%

Question 2

What strategies for parents prevent RSV?

Answer 2

1. Avoid contact with individuals with respiratory tract infections whenever possible
2. Hand hygiene
3. Breastfeeding
4. Avoid cigarette smoke

Question 3

What is palivizumab?

Answer 3

Humanized murine monoclonal IgG-1 directed against epitope on the F glycoprotein RSV

Question 4

What are serious adverse reactions to palivizumab?

Answer 4

Anaphylaxis (rare)

Question 5

What is the standard dosing of palivizumab?

Answer 5

15mg/kg IM q30d x 5 doses (max) during RSV season

Question 6

What is the drug costs for palivizumab five doses in an infant ~5kg?

Answer 6

$5600

Question 7

What factors makes the use of palivizumab in healthy preterm questionable?

Answer 7

1. Although RSV hospitalization rates correlate with GA, the magnitude of difference between preterm infants without CLD and term infants does not warrant routine use of palivizumab, except possibly in very preterm infants. RSV hospitalization rates without palivizumab that are significantly lower than for infants with CHD or CLD. Even in infants born before 30 weeks’ GA, admission rates were <10% in all but one study. The main limitation of Figure 3 is that, as with Figures 1 and 2, case findings were incomplete in some studies, but this proviso should have applied equally to all GAs.
2. There have been significant advances in neonatology, such that infants with or without CLD are now healthier and have less residual lung damage than did infants of the same GA in the past.
3. The parents of fragile infants are now more aware of the principles of infection transmission than in decades past. Parental leaves are longer and there are fewer young infants in child care settings, where the risk of RSV acquisition is higher.

Question 8

What is the cost effectiveness of palivizumab?

Answer 8

Palivizumab is unlikely to be cost-effective in children with prematurity, CLD or CHD, and can only be potentially cost-effective in settings where RSV hospitalizations are exceedingly common and very expensive (such as Inuit infants in rural Baffin Island).

Question 9

What are the recommendations for palivizumab in different risk groups?

Answer 9

1. Children with hemodynamically significant CHD or CLD (defined as a need for oxygen at 36 weeks’ GA) who require ongoing diuretics, bronchodilators, steroids or supplemental oxygen, should receive palivizumab if they are <12 months of age at the start of RSV season. Because the incidence of RSV decreases in the second year of life, palivizumab is not indicated during the second RSV season for infants with CHD or for the vast majority of children with CLD (with the exception of those still on or weaned off of supplemental oxygen in the past three months).
2. In preterm infants without CLD born before 30 + 0 weeks’ GA who are <6 months of age at the start of RSV season, it is reasonable (but not essential) to offer palivizumab. Infants born after 30 + 0 weeks’ GA have RSV admission rates that are consistently ≤7% (Figure 3), yielding a minimum number needed to treat of 18 (90 doses of palivizumab to prevent one RSV admission) if one assumes 80% efficacy and five doses per infant. Therefore, palivizumab should not be prescribed for this group.
3. Infants in remote communities who would require air transportation for hospitalization born before 36 + 0 weeks’ GA and <6 months of age at the start of RSV season should be offered palivizumab. It is not clear whether this recommendation should apply only to Inuit infants, to all Aboriginal infants or to all infants in remote communities. The incidence of RSV hospitalization in a remote community in previous years should be taken into account when making this decision. A practical issue is that the onset and duration of RSV season is unpredictable in the Far North. A logical option is to delay administering palivizumab until RSV is detected in the Far North. The attendant risk is that significant spread may have already occurred. Consideration may be given to administering palivizumab during RSV season to term Inuit infants until they reach six months of age only if they live in communities with documented persistent high rates of RSV hospitalization. However, the first priority should be to provide palivizumab to infants with prematurity, CLD or CHD.
4. Children with immunodeficiencies, Down syndrome, cystic fibrosis, upper airway obstruction or a chronic pulmonary disease other than CLD should not routinely be offered palivizumab. However, prophylaxis may be considered for children <24 months of age who are on home oxygen, have had a prolonged hospitalization for severe pulmonary disease or are severely immunocompromised.
5. Continuation of monthly palivizumab is not recommended for children hospitalized with breakthrough RSV infection. Repeat RSV infections in one season are not common. Although recommended on the product monograph, the number needed to treat is no doubt very high if one continues palivizumab following RSV infection.

Question 10

What are the recommendations for optimization of palivizumab programs?

Answer 10

1. For eligible infants being discharged home for the first time during RSV season, palivizumab should be started just before discharge. Use before discharge to prevent nosocomial RSV is an expensive strategy that is not recommended.
2. Programs should administer a maximum of three to five doses, with four doses probably being sufficient in all risk groups if palivizumab is started only when there is RSV activity in the community, especially if doses 2, 3, and 4 are given 38 days apart.
3. There is no evidence to support giving >5 doses in one RSV season, administration to any child >24 months of age at the start of RSV season, or using palivizumab as RSV therapy.
4. A panel of experts should be convened in each province or territory to review annually the palivizumab program guidelines and outcomes