krilov_edit.qxp 13/11/07 11:40 Page 36
Respiratory Syncytial Virus
directed against a conserved region of the F protein of RSV, was proved to An additional important aspect of RSV LRTI in infancy relates to potential
be safe and effective in the prevention of severe RSV infection long-term sequelae. An association between RSV LRTI in infancy and
(hospitalization) in high-risk infants with prematurity ± CLD, decreasing subsequent episodes of wheezing over the next ≥10 years has been clearly
RSV hospitalization rates from 10.6% in placebo recipients to 4.8% in established.
25,26
It is uncertain, however, whether the virus contributes to
palivizumab-treated babies.
19
A similar trial with this monoclonal antibody airway and/or immunological changes that predispose to later wheezing, or
in infants with hemodynamically significant congenital heart disease
(CHD) also demonstrated safety and efficacy.
20
Post-licensure follow-up
has demonstrated continued low hospitalization rates in high-risk infants Recent preliminary data in premature
receiving palivizumab prophylaxis.
21
Clinical isolates of RSV resistant to
infants suggest that those receiving
palivizumab have not been reported. Guidelines for the use of palivzumab
in the US published in 2006 are outlined in Table 3.
22
palivizumab had fewer medically
attended respiratory illnesses than
A second-generation monoclonal antibody, motavizumab, which is derived
from palivizumab, is currently in clinical trials in comparison with non-prophylaxed controls over two
palivizumab for safety and efficacy. Motavizumab is 20–100-fold more
to three years.
active against RSV in vitro and in animal models of RSV infection. A
preliminary analysis of >6,600 premature infants randomized to receive
motavizumab or palivizumab prophylaxis for five monthly injections in a whether the severity of the initial RSV infection reflects the individual’s
single RSV season demonstrated non-inferiority of motavizumab for propensity to wheezing, which would have occurred unrelated to the early
decreasing hospitalizations and significantly fewer medically attended RSV LRTI.
27,28
Recent preliminary data in premature infants suggest that those
respiratory illnesses in the motavizumab recipients.
23
receiving palivizumab had fewer medically attended respiratory illnesses than
non-prophylaxed controls over two to three years.
29
Further verification of
The development of a vaccine to provide active immunization against severe these findings will be important in devising future RSV prevention strategies.
RSV infection for all infants remains an unmet challenge. An early formalin-
inactivated RSV vaccine was associated with enhanced disease after natural In conclusion, on this, the golden anniversary of the discovery of RSV, much
infection. More recently, approaches to RSV vaccine development have has been accomplished in the understanding and management of this
focused on subunit protein or live attenuated viral vaccines.
24
Although early important infection. Still, there remains important work to do in order to
clinical evaluations of candidate vaccines are ongoing, the extent of safety alleviate the toll of RSV infection on human suffering. In future, I hope we
and efficacy data needed is such that there is not likely to be an RSV vaccine can celebrate further advances that will have led to major inroads in
available for widespread use in the near future. controlling this infection for all infants and children. ■
1. Morris JA, Blant RE Jr, Savage RE, Recovery of cytopathogenic In: Fields RN, Knipe DM, Howley PM, et al., Fields virology (5th 20. Feltes TF, Cabalka AK, Meissner HC, et al., Palivizumab prophylaxis
agent from chimpanzees with coryza, Proc Soc Exp Bio Med, edn), Philadelphia, PA: Lippincott-Roven Publishers, 2007: reduces hospitalization due to respiratory syncytial virus in young
1956;92:544–50. 1601–40. children with hemodynamically significant congenital heart
2. Chancock R, Finberg L, Recovery from infants with respiratory 12. Shetty AK, Tregnor E, Hill DW, et al., Comparison of conversional diseases, J Pediatr, 2003;143:532–40.
illness of a virus related to chimpanzee coryza agent (CCA). II. viral cultures with direct fluorescent antibody stairs for diagnosis 21. Romero JR, Palivizumab prophylaxis of respiratory syncytial virus
Epidemiologic aspects of infection in infants and young children, of community-acquired respiratory infections in hospitalized disease form 1998 to 2002: Results from four years of
Am J Hyg, 1957;66:291–300. children, Pediatric Infect Dis J, 2003;22:789–94. palivizumab usage, Pediatric Infect Dis J, 2003;22(Suppl. 2):
3. Glezen WP, Taber LH, Frank AC, Kasel JA, Risk of primary infection 13. Perkins SM, Webb DL, Torrance SA, et al., Comparison of a real- 546–54.
and reinfection with respiratory syncytial virus, Am J Dis Child, time reverse transcriptase PCR assay and a culture technique for 22. American Academy of Pediatrics, Respiratory Syncytial Virus. In:
1986;140:543–6. quantitative assessment of viral load in children naturally infected Pickering CK, Baker CJ, Lung SS, McMillan JA (eds), Red Book:
4. Falsey AR, Hennessey P, Formia MR, et al., Respiratory syncytial with respiratory syncytial virus, J Clin Microbiol, 2005;43: 2006 Report of the Committee on Infectious Diseases (27th edn),
virus infection in elderly and high risk adults, N Engl J Med, 2356–62. Elk Grove, IL: American Academy of Pediatrics, 2006;560–66.
2005;352:1749–59. 14. Subcommittee on Diagnosis and Management of Bronchiolitis, 23. Carbonell X, Losonsky G, Micki H, et al., Phase 3 trial of
5. Shay DK, Holman RC, Newman RD, et al., Bronchiolitis-associated Diagnosis and management of bronchiolitis, Pediatrics, motavizumab (MED 1-524) an enhanced potency respiratory
hospitalization among US children, 1980–1996, JAMA, 1999;282: 2006;118:1774–93. syncytial virus (RSV) specific monoclonal antibody (Mab) for
1440–46. 15. Corneli HM, Zorc JJ, Majahan P, et al., A multicenter randomized prevention of serious RSV disease in high risk infants, Pediatric
6. Leader S, Kohlhase K, Recent trends in severe respiratory syncytial controlled trial of dexamethasone for bronchiolitis, N Engl J Med, Academic Societies Meeting, 2007; abstract 8220.9.
virus (RSV) among US infants, 1997 to 2000, J Pediatr, 2003;143 2007;357:331–9. 24. Maggon K, Barik S, New drugs and treatment for respiratory
(Suppl. 5):S127–S132. 16. Greenes DS, Harper MB, Low risk of bacteria in febrile children syncytial virus, Rev Med Virol, 2004;14:149–68.
7. Hall CB, Walsh EE, Schnabel KS, et al., Occurrence of groups A and with recognized viral syndromes, Pediatric Infect Dis J, 1999;18: 25. Sigurs N, Gustafsson PM, Bjarnason R, et al., Severe RSV
B of respiratory syncytial virus over 15 years: associated 258–61. bronchiolitis in infancy and asthma and allergy at age 13,
epidemiologic and clinical characteristics in hospitalized and 17. Hall CB, Powell KR, Schnabel KC, et al., Risk of serious bacterial Am J Resp Crit Care Med, 2005;171:137–41.
ambulatory children, J Infect Dis, 1990;162:1283–90. infection in infants hospitalized with respiratory syncytial viral 26. Stein RJ, Sherrill D, Morgan WJ, et al., RSV in early life and risk of
8. Hall CB, Douglas G Jr, Modes of transmission of respiratory infection, J Pediatr, 1988;113:266–71. wheeze and allergy by 13 years, Lancet, 1999;354:541–5.
syncytial virus, J Pediatr, 1981;99:100–103. 18. The Prevent Study Group, Reduction of respiratory syncytial virus 27. Martinez FD, Heterogeneity of the association between lower
9. McConnochie KM, Roghmann KJ, Parents smoking, presence of hospitalization among premature infants and infants with respiratory illness in infancy and subsequent asthma, Proc Am Thor
older siblings, and family history of asthma increase risk of bronchopulmonary dysplasia using respiratory syncytial virus Soc, 2005;2:157–61.
bronchiolitis, Am J Dis Child, 1986;140:806–12. immune globulin prophylaxis, Pediatrics, 1997;99:93–9. 28. Meissner HC, Long SS, Respiratory syncytial virus infection and
10. Holberg CJ, Wright AL, Martinez FD, et al., Risk factors for 19. Impact-RSV Study Group, Palivizumab, a humanized respiratory recurrent wheezing; a complex relationship, J Pediatr, 2007;151:6–7.
respiratory syncytial virus-associated lower respiratory illnesses in syncytial virus monoclonal antibody, reduces hospitalization from 29. Simoes EF, Groothuis JR, Carbonell-Strany X, et al., Palivizumab
the first year of life, Am J Epidemiol, 1991;133:1135–7. respiratory syncytial virus infection in high risk infants, Pediatrics, prophylaxis, respiratory syncytial virus and subsequent recurrent
11. Collins PL, McIntosh K, Chanock RM, Respiratory syncytial virus. 1998;102:531–2. wheezing, J Pediatr, 2007;151:34–42.
36 US INFECTIOUS DISEASE 2007
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68