A Novel Six Consecutive Monthly Doses of Palivizumab Prophylaxis Protocol for the Prevention of Respiratory Syncytial Virus Infection in High-Risk Preterm Infants in Taiwan
Background Respiratory syncytial virus (RSV) circulates year round in Taiwan. A novel six consecutive monthly doses of palivizumab for RSV prevention protocol has been approved for high risk preterm infants since December 2010. This study aimed to determine the clinical effectiveness and safety of this novel protocol for the prevention of RSV infection. Methods From April 2011 to March 2013, we enrolled infants born at ≤28 weeks gestation and infants born at ≤35 weeks gestation with chronic lung disease (CLD) who received palivizumab prophylaxis as study group and followed up for 12 months. Historic control, those who were born and followed up between July 2000 and June 2008, were retrieved for propensity score matching. Primary endpoint was RSV-related hospitalization, and secondary endpoints included the length of hospital stay and intensive care unit (ICU) care. Results We enrolled 127 infants (108 infants born at ≤28 weeks and 19 infants born at 29–35 weeks with CLD). They completed 6-dose palivizumab as scheduled. Among the study group, the RSV-related hospitalizations were 2 (1.6%) within 6 months and 5 (3.9%) within 12 months after discharge. We matched 127 infants in the control group with 127 infants in the study group by propensity score matching. The reduction of RSV-related hospitalization rates were 86% (10.2% vs 1.6%, p = 0.002) within 6 months after discharge and 78% (15.7% vs 3.9%, p = 0.004) within 12 months after discharge. Compared to the control group, the rate of ICU care significantly decreased from 7.1% to 0.8% (p = 0.024) within 6 months after discharge and from 7.9% to 0.8% (p = 0.014) within 12 months after discharge. Adverse events were recorded in 6.4% injections. Conclusions Six monthly intramuscular administration of palivizumab is effective for prevention of RSV hospitalization in regions with no single seasonal peak of RSV infection such as Taiwan.
References
[1]
Hall CB (2010) Respiratory Syncytial Virus. In: Mandell GL BJ, Dolin R, editor. Principles and Practice of Infectious Diseases. 7 ed. New York: Churchill Livingstone Inc. 2207–2221.
Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, et al. (1999) Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 282: 1440–1446. doi: 10.1001/jama.282.15.1440
[4]
Cilla G, Sarasua A, Montes M, Arostegui N, Vicente D, et al. (2006) Risk factors for hospitalization due to respiratory syncytial virus infection among infants in the Basque Country, Spain. Epidemiol Infect 134: 506–513. doi: 10.1017/s0950268805005571
[5]
Chi H, Chang IS, Tsai FY, Huang LM, Shao PL, et al. (2011) Epidemiological study of hospitalization associated with respiratory syncytial virus infection in Taiwanese children between 2004 and 2007. J Formos Med Assoc 110: 388–396. doi: 10.1016/s0929-6646(11)60057-0
[6]
Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, et al. (2009) The burden of respiratory syncytial virus infection in young children. N Engl J Med 360: 588–598. doi: 10.1056/nejmoa0804877
[7]
Sommer C, Resch B, Simoes EA (2011) Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J 5: 144–154. doi: 10.2174/1874285801105010144
[8]
Joffe S, Escobar GJ, Black SB, Armstrong MA, Lieu TA (1999) Rehospitalization for respiratory syncytial virus among premature infants. Pediatrics 104: 894–899. doi: 10.1542/peds.104.4.894
[9]
Carbonell-Estrany X, Quero J, Bustos G, Cotero A, Domenech E, et al. (2000) Rehospitalization because of respiratory syncytial virus infection in premature infants younger than 33 weeks of gestation: a prospective study. IRIS Study Group. Pediatr Infect Dis J 19: 592–597. doi: 10.1097/00006454-200007000-00002
[10]
Underwood MA, Danielsen B, Gilbert WM (2007) Cost, causes and rates of rehospitalization of preterm infants. J Perinatol 27: 614–619. doi: 10.1038/sj.jp.7211801
[11]
Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, et al. (1997) Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis 176: 1215–1224. doi: 10.1086/514115
[12]
American Academy of Pediatrics (1998) Committee on Infectious Diseases and Committee of Fetus and Newborn (1998) Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV. Pediatrics 102: 1211–1216. doi: 10.1542/peds.102.5.1211
[13]
American Academy of Pediatrics (2003) Committee on Infectious Diseases and Committee of Fetus and Newborn (2003) Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 112: 1442–1446. doi: 10.1542/peds.112.6.1442
[14]
American Academy of Pediatrics (2009) Committee on Infectious Diseases and Committee of Fetus and Newborn (2009) Policy statements–Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics 124: 1694–1701. doi: 10.1542/peds.2009-2345
[15]
Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, et al. (2007) Influenza- and RSV-associated hospitalizations among adults. Vaccine 25: 846–855. doi: 10.1016/j.vaccine.2006.09.041
[16]
Elhassan NO, Sorbero ME, Hall CB, Stevens TP, Dick AW (2006) Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease. Arch Pediatr Adolesc Med 160: 1070–1076. doi: 10.1001/archpedi.160.10.1070
[17]
Wegner S, Vann JJ, Liu G, Byrns P, Cypra C, et al. (2004) Direct cost analyses of palivizumab treatment in a cohort of at-risk children: evidence from the North Carolina Medicaid Program. Pediatrics 114: 1612–1619. doi: 10.1542/peds.2004-0959
[18]
Loscertales MP, Roca A, Ventura PJ, Abacassamo F, Dos Santos F, et al. (2002) Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique. Pediatr Infect Dis J 21: 148–155. doi: 10.1097/00006454-200202000-00013
[19]
Stensballe LG, Devasundaram JK, Simoes EA (2003) Respiratory syncytial virus epidemics: the ups and downs of a seasonal virus. Pediatr Infect Dis J 22: S21–32. doi: 10.1097/01.inf.0000053882.70365.c9
[20]
Meissner HC, Anderson LJ, Pickering LK (2004) Annual variation in respiratory syncytial virus season and decisions regarding immunoprophylaxis with palivizumab. Pediatrics 114: 1082–1084. doi: 10.1542/peds.2004-1300
[21]
Rossi GA, Medici MC, Arcangeletti MC, Lanari M, Merolla R, et al. (2007) Risk factors for severe RSV-induced lower respiratory tract infection over four consecutive epidemics. Eur J Pediatr 166: 1267–1272. doi: 10.1007/s00431-007-0418-y
[22]
Lee JT, Chang LY, Wang LC, Kao CL, Shao PL, et al. (2007) Epidemiology of respiratory syncytial virus infection in northern Taiwan, 2001–2005 – seasonality, clinical characteristics, and disease burden. J Microbiol Immunol Infect 40: 293–301.
[23]
Tsai HP, Kuo PH, Liu CC, Wang JR (2001) Respiratory viral infections among pediatric inpatients and outpatients in Taiwan from 1997 to 1999. J Clin Microbiol 39: 111–118. doi: 10.1128/jcm.39.1.111-118.2001
[24]
Austin PC (2008) Assessing balance in measured baseline covariates when using many-to-one matching on the propensity-score. Pharmacoepidemiol Drug Saf 17: 1218–1225. doi: 10.1002/pds.1674
[25]
Frogel M, Nerwen C, Cohen A, VanVeldhuisen P, Harrington M, et al. (2008) Prevention of hospitalization due to respiratory syncytial virus: results from the Palivizumab Outcomes Registry. J Perinatol 28: 511–517. doi: 10.1038/jp.2008.28
[26]
Grimaldi M, Gouyon B, Sagot P, Quantin C, Huet F, et al. (2007) Palivizumab efficacy in preterm infants with gestational age < or = 30 weeks without bronchopulmonary dysplasia. Pediatr Pulmonol 42: 189–192. doi: 10.1002/ppul.20503
[27]
Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, Quero J (2003) Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J 22: 823–827. doi: 10.1097/01.inf.0000086403.50417.7c
[28]
Singleton R, Dooley L, Bruden D, Raelson S, Butler JC (2003) Impact of palivizumab prophylaxis on respiratory syncytial virus hospitalizations in high risk Alaska Native infants. Pediatr Infect Dis J 22: 540–545. doi: 10.1097/01.inf.0000069768.34383.18
[29]
The IMpact-RSV Study Group (1998) Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. Pediatrics 102: 531–537. doi: 10.1542/peds.102.3.531
[30]
Saez-Llorens X, Moreno MT, Ramilo O, Sanchez PJ, Top FH Jr, et al. (2004) Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection. Pediatr Infect Dis J 23: 707–712. doi: 10.1097/01.inf.0000133165.85909.08
[31]
Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK (2012) Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children. Antimicrob Agents Chemother 56: 4927–4936. doi: 10.1128/aac.06446-11
[32]
Fryzek JP, Martone WJ, Groothuis JR (2011) Trends in chronologic age and infant respiratory syncytial virus hospitalization: an 8-year cohort study. Adv Ther 28: 195–201. doi: 10.1007/s12325-010-0106-6
[33]
Bont L, Houben ML (2011) Commentary: why are young healthy term infants protected against respiratory syncytial virus bronchiolitis? Pediatr Infect Dis J 30: 785–786. doi: 10.1097/inf.0b013e31821fef9e
[34]
Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR (2000) Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr 137: 865–870. doi: 10.1067/mpd.2000.110531
[35]
Chew FT, Doraisingham S, Ling AE, Kumarasinghe G, Lee BW (1998) Seasonal trends of viral respiratory tract infections in the tropics. Epidemiol Infect 121: 121–128. doi: 10.1017/s0950268898008905
[36]
Chan PW, Chew FT, Tan TN, Chua KB, Hooi PS (2002) Seasonal variation in respiratory syncytial virus chest infection in the tropics. Pediatr Pulmonol 34: 47–51. doi: 10.1002/ppul.10095
[37]
Yusuf S, Piedimonte G, Auais A, Demmler G, Krishnan S, et al. (2007) The relationship of meteorological conditions to the epidemic activity of respiratory syncytial virus. Epidemiol Infect 135: 1077–1090. doi: 10.1017/s095026880600776x
[38]
Romero JR (2003) Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: results from four years of palivizumab usage. Pediatr Infect Dis J 22: S46–54. doi: 10.1097/01.inf.0000053885.34703.84
[39]
Mitchell I, Paes BA, Li A, Lanctot KL (2011) CARESS: the Canadian registry of palivizumab. Pediatr Infect Dis J 30: 651–655. doi: 10.1097/inf.0b013e31821146f7
[40]
Groothuis JR (2001) Safety and tolerance of palivizumab administration in a large Northern Hemisphere trial. Northern Hemisphere Expanded Access Study Group. Pediatr Infect Dis J 20: 628–630. doi: 10.1097/00006454-200106000-00018
