Journal of Medical Virology 87:1285–1291 (2015)
Value of a Risk Scoring Tool to Predict Respiratory Syncytial Virus Disease Severity and Need for Hospitalization in Term Infants Rafat Mosalli,1* Asmaa Mostafa Abdul Moez,2 Mohammed Janish,3 and Bosco Paes4 1
Department of Pediatrics, Umm Al Qura University, Mecca, Saudi Arabia Department of Pediatrics, International Medical Center, Jeddah, Saudi Arabia 3 Research Center, International Medical Center, Jeddah, Saudi Arabia 4 Department of Pediatrics (Neonatal Division), McMaster University, Hamilton, Ontario, Canada 2
Several environmental and demographic risk factors have been validated and are used to determine the risk of acquiring severe respiratory syncytial virus (RSV) infection and subsequent hospitalization in late preterm infants born at 33–35 weeks gestational age. The applicability of the same composite model of risk factors in the term population has not been fully explored. The primary objective of this pilot study was to establish whether a risk scoring tool (RST), could predict the severity of RSV infection in term, RSV-positive infants who were hospitalized. A retrospective observational study was conducted in a pediatric unit, over 2 RSV seasons (2011–2013). A convenient sample of 72 children was selected out of a total of 111 RSVpositive cases after exclusions. The RST was applied and a score of respiratory disease severity was determined for each patient. Demographic characteristics were analyzed by standard descriptive methods, x2 analysis was utilized for categorical data and ANOVA for comparison between the clinical severity groups and the RST score. A P-value 1 smoker in the home Total Score/100
25 17 13 12 12 11 10
0 0 0 0 0 0 0
Score rating: Low risk (0–48), Moderate risk (49–64), High risk (65–100). Infants with a RST score of 49–100 qualify for RSV prophylaxis. * Adapted from Sampalis et al. [2008].
J. Med. Virol. DOI 10.1002/jmv
Predicting RSV Hospitalization in Term Infants
1287
TABLE II. Kristjansson Respiratory Score Rating for Acute Bronchiolitis Score
Respiratory rate (breaths/minute)
0 1
60
Chest recession
Breath sounds
Skin color
General conditiona
None Moderate (costodiaphragmatic) Severe (as in 1 þ rib þ jugular retraction
Vesicular Wheeze rhonchi/rales Severe wheeze rhonchi/rales
Normal Pallor
Mild Moderate
Cyanosis
Severe
Adapted from Kristj ansson et al. [1993]. a Mild (activity þ feeding is normal); Moderate (activity and feeding is less than normal); Severe (child is ill and feeds poorly)
detects both viable and non-viable RSV. Test performance depends on the antigen load in the collected specimen and involves a rapid immunochromatographic analysis of the nasopharyngeal lavage. The overall sensitivity of the test is 70–93% while the specificity ranges from 89%–100% [Blyth et al., 2011]. All RSV positive cases were reported weekly to the study co-ordinator by the virology laboratory. STATISTICAL ANALYSIS Data were entered into a standard statistical program (SPSS, IBM, Version 19) and analyzed using descriptive statistics. Means, standard deviations (SDs), and percentage were used to analyze demographics and RST scores for all hospitalized patients based on severity. Chi-square and ANOVA were employed to compare the RSV clinical severity rating and the RST score. A P-value 0.05) and the largest percentage of infants (60%) hospitalized for RSV lower respiratory tract infection received a low-risk score on the RST and would not have qualified for prophylaxis (Table I). Of interest, the mean age of presentation with lower respiratory tract infection-related hospitalization was 7.4 months and the older age (6months) is in agreement with some population based studies reported in the literature [Nair et al., 2010; Houben et al., 2011; Sim~oes et al., 2011]. Several reasons may account for the results of this study. First, the sample size of the pilot project was
relatively small. However, similar findings were also documented by Paes et al. [2009] who found that the RST did not discriminate between low versus moderate to high-risk RSV-positive term infants who required hospitalization. In the current study, there was additionally a mismatch between the validated, clinical Kristjansson severity rating, and the robust RST model where infants with the mildest respiratory symptomatology had the highest mean scores (47). Second, it is likely that other risk factors as identified by Houben et al. [2011] may be more significant in the term population. Figueras-Aloy et al. [2004] noted that the risk factors for RSV hospitalization in a retrospective study (FLIP-1) involving 33–35 weeks’ gestational age infants did not concur with those found in a prospective study [Figueras-Aloy et al., 2008; FLIP-2] that enrolled infants who were 32–35 weeks. This was in part due to study design but the inclusion of one extra week (infants who were 32 weeks gestational age) in the latter study may have influenced the results. This supports the premise that risk factor models that have good predictive value for RSV-related hospitalization in a defined subset of preterm infants should not be loosely applied to others of varying gestational ages with the expectation of similar outcomes. Last, socio-economic status, country-specific epidemiological, and environmental risk factors not included in the Canadian risk scoring tool may have reduced the predictive power to detect RSV-related hospitalization [Sampalis et al., 2008]. In conclusion, the RST prove to have limited value in the prediction of RSV-related hospitalization in term infants, nor did it correlate with the clinical severity of illness. The absence of positive trends in the results indicates that a larger study based on a similar hypothesis, irrespective of the risk scoring model utilized, is likely to yield similar findings. Targeting approximately 8% of a universally large term birth cohort, which was reported by Houben et al. [2011] to be at highest risk for RSV lower respiratory tract infection for prophylaxis is also not J. Med. Virol. DOI 10.1002/jmv
1290
Mosalli et al.
cost-effective. Further studies are needed to consolidate a model that best predicts severe RSV disease in this population and subsequent hospitalization. REFERENCES Blanken MO, Koffijberg H, Nibbelke EE, Rovers MM, Bont L. Dutch RSV Neonatal Network. 2013. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: A multicenter birth cohort study. PLoS ONE 8:e59161. Blyth CC, Booy R, Dwyer DE. 2011. Point of care testing: Diagnosis outside the virology laboratory. Methods Mol Biol 665:415– 433. 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. Butt ML, Symington A, Janes M, Elliott L, Steele S, Paes BA. 2011. The impact of prophylaxis on paediatric intensive care unit admissions for RSV infection: A retrospective, single-centre study. Eur J Pediatr 170:907–913. Chin HJ, Seng QB. 2004. Reliability and validity of the respiratory score in the assessment of acute bronchiolitis. Malays J Med Sci 11:34–40. Feng L, Li Z, Zhao S, Nair H, Lai S, Xu W, Li M, Wu J, Ren L, Liu W, Yuan Z, Chen Y, Wang X, Zhao Z, Zhang H, Li F, Ye X, Li S, Feikin D, Yu H, Yang W. 2014. Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013. PLoS ONE 9:e99419. Figueras-Aloy J, Carbonell-Estrany X, Quero J. IRIS Study Group. 2004. Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33-35 weeks in Spain. Pediatr Infect Dis J 23:815–820. Figueras-Aloy J, Carbonell-Estrany X, Quero-Jim enez J, Fern andez-Colomer B, Guzm an-Caba~ nas J, Echaniz-Urcelay I. Domenech-Martnez E; IRIS Study Group. 2008. FLIP-2 Study: Risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks. Pediatr Infect Dis J 27:788– 793. Frogel M, Nerwen C, Cohen A, VanVeldhuisen P, Harrington M, Boron M. Palivizumab Outcomes Registry Group. 2008. Prevention of hospitalization due to respiratory syncytial virus: Results from the Palivizumab Outcomes Registry. J Perinatol 28:511– 517. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P. 2009. The burden of respiratory syncytial virus infection in young children. N Engl J Med 360:588–598. Hasegawa K, Mansbach JM, Teach SJ, Fisher ES, Hershey D, Koh JY, Clark S, Piedra PA, Sullivan AF, Camargo CA, Jr. 2014. Multicenter study of viral etiology and relapse in hospitalized children with bronchiolitis. Pediatr Infect Dis J 33:809– 813. € R, Ruuskanen Heikkinen T, Valkonen H, Lehtonen L, Vainionp€ aa O. 2005. Hospital admission of high risk infants for respiratory syncytial virus infection: Implications for palivizumab prophylaxis. Arch Dis Child Fetal Neonatal Ed 90:F64–F68. Horn SD, Smout RJ. 2003. Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr 143:S133–S141. Houben ML, Bont L, Wilbrink B, Belderbos ME, Kimpen JL, Visser GH, Rovers MM. 2011. Clinical prediction rule for RSV bronchiolitis in healthy newborns: prognostic birth cohort study. Pediatrics 127:35–41. Kristj ansson S, Lødrup Carlsen KC, Wennergren G, Strannega˚rd IL, Carlsen KH. 1993. Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers. Arch Dis Child 69:650–654. Kusuda S, Takahashi N, Saitoh T, Terai M, Kaneda H, Kato Y, Ohashi A, Watabe S, Joh-o K, Hirai K. 2011. Survey of pediatric ward hospitalization due to respiratory syncytial virus infection after the introduction of palivizumab to high-risk infants in Japan. Pediatr Int 53:368–373.
J. Med. Virol. DOI 10.1002/jmv
Lanct^ ot KL, Masoud ST, Paes BA, Tarride JE, Chiu A, Hui C, Francis PL, Oh PI. 2008. The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: A Canadian-based analysis. Curr Med Res Opin 24:3223–3237. Langley JM, Wang EE, Law BJ, Stephens D, Boucher FD, Dobson S, McDonald J, MacDonald NE, Mitchell I, Robinson JL. 1997. Economic evaluation of respiratory syncytial virus infection in Canadian children: a Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study. J Pediatr 131:113–117. Langley GF, Anderson LJ. 2011. Epidemiology and prevention of respiratory syncytial virus infections among infants and young children. Pediatr Infect Dis J 30:510–517. Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I, Sampalis J, Walti H, Robinson J, O’Brien K, Majaesic C, Caouette G, Frenette L, Le Saux N, Simmons B, Moisiuk S, Sankaran K, Ojah C, Singh AJ, Lebel MH, Bacheyie GS, Onyett H, Michaliszyn A, Manzi P, Parison D. 2004. The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J 23:806–814. Makari D, Hoopes JM, White N. 2009. Impact of RSV: Implications for managed care. Manag Care 18:2–7. Mansbach JM, Piedra PA, Teach SJ, Sullivan AF, Forgey T, Clark S, Espinola JA, Camargo CA, Jr. MARC-30 Investigators. 2012. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med 166:700–706. Miron D, Srugo I, Kra-Oz Z, Keness Y, Wolf D, Amirav I, Kassis I. 2010. Sole pathogen in acute bronchiolitis: Is there a role for other organisms apart from respiratory syncytial virus? Pediatr Infect Dis J 29:e7–e10. Moreno-Perez D, Calvo C. Five Study Group. 2014. Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study. Influenza Other Respir Viruses 8:209–216. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O’Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Sim~ oes EA, Rudan I, Weber MW, Campbell H. 2010. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 375: 1545–1555. Navas L, Wang E, de Carvalho V, Robinson J. 1992. Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. J Pediatr 121:348–354. Paes B, Cole M, Latchman A, Pinelli J. 2009. Predictive value of the respiratory syncytial virus risk-scoring tool in the term infant in Canada. Curr Med Res Opin 25:2191–2196. Paes BA, Mitchell I, Banerji A, Lanct^ot KL, Langley JM. 2011. A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice. Can Respir J 18:e10–e19. Paes B, Mitchell I, Li A, Harimoto T, Lanct^ ot KL. 2013. Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005-2012) compared to other international registries. Clin Dev Immunol 2013:917068. Prais D, Danino D, Schonfeld T, Amir J. 2005. Impact of palivizumab on admission to the ICU for respiratory syncytial virus bronchiolitis: A national survey. Chest 128:2765–2771. Rudan I, O’Brien KL, Nair H, Liu L, Theodoratou E, Qazi S, Luksic I, Fischer Walker CL, Black RE, Campbell H. Child Health Epidemiology Reference Group (CHERG). 2013. Epidemiology and etiology of childhood pneumonia in 2010: Estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Glob Health 3:010401. Sampalis JS, Langley J, Carbonell-Estrany X, Paes B, O’Brien K, Allen U, Mitchell I, Aloy JF, Pedraz C, Michaliszyn AF. 2008. Development and validation of a risk scoring tool to predict respiratory syncytial virus hospitalization in premature infants born at 33 through 35 completed weeks of gestation. Med Decis Making 28:471–480.
Predicting RSV Hospitalization in Term Infants Sim~oes EA, Carbonell-Estrany X, Fullarton JR, Liese JG, FiguerasAloy J, Doering G, Guzman J. European RSV Risk Factor Study Group. 2008. A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33-35 weeks of gestational age, based on data from the Spanish FLIP Study. Respir Res 9:78. Sim~ oes EA, Mutyara K, Soh S, Agustian D, Hibberd ML, Kartasasmita CB. 2011. The epidemiology of respiratory syncytial virus lower respiratory tract infections in children less than 5 years of age in Indonesia. Pediatr Infect Dis J 30:778–784.
1291 Sommer C, Resch B, Sim~ oes EA. 2011. Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J 5:144–154. Thorburn K. 2009. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child 94:99–103. Willson DF, Landrigan CP, Horn SD, Smout RJ. 2003. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 143:S142–S149.
J. Med. Virol. DOI 10.1002/jmv
Value of a Risk Scoring Tool to Predict Respiratory Syncytial Virus Disease Severity and Need for Hospitalization in Term Infants Rafat Mosalli,1* Asmaa Mostafa Abdul Moez,2 Mohammed Janish,3 and Bosco Paes4 1
Department of Pediatrics, Umm Al Qura University, Mecca, Saudi Arabia Department of Pediatrics, International Medical Center, Jeddah, Saudi Arabia 3 Research Center, International Medical Center, Jeddah, Saudi Arabia 4 Department of Pediatrics (Neonatal Division), McMaster University, Hamilton, Ontario, Canada 2
Several environmental and demographic risk factors have been validated and are used to determine the risk of acquiring severe respiratory syncytial virus (RSV) infection and subsequent hospitalization in late preterm infants born at 33–35 weeks gestational age. The applicability of the same composite model of risk factors in the term population has not been fully explored. The primary objective of this pilot study was to establish whether a risk scoring tool (RST), could predict the severity of RSV infection in term, RSV-positive infants who were hospitalized. A retrospective observational study was conducted in a pediatric unit, over 2 RSV seasons (2011–2013). A convenient sample of 72 children was selected out of a total of 111 RSVpositive cases after exclusions. The RST was applied and a score of respiratory disease severity was determined for each patient. Demographic characteristics were analyzed by standard descriptive methods, x2 analysis was utilized for categorical data and ANOVA for comparison between the clinical severity groups and the RST score. A P-value 1 smoker in the home Total Score/100
25 17 13 12 12 11 10
0 0 0 0 0 0 0
Score rating: Low risk (0–48), Moderate risk (49–64), High risk (65–100). Infants with a RST score of 49–100 qualify for RSV prophylaxis. * Adapted from Sampalis et al. [2008].
J. Med. Virol. DOI 10.1002/jmv
Predicting RSV Hospitalization in Term Infants
1287
TABLE II. Kristjansson Respiratory Score Rating for Acute Bronchiolitis Score
Respiratory rate (breaths/minute)
0 1
60
Chest recession
Breath sounds
Skin color
General conditiona
None Moderate (costodiaphragmatic) Severe (as in 1 þ rib þ jugular retraction
Vesicular Wheeze rhonchi/rales Severe wheeze rhonchi/rales
Normal Pallor
Mild Moderate
Cyanosis
Severe
Adapted from Kristj ansson et al. [1993]. a Mild (activity þ feeding is normal); Moderate (activity and feeding is less than normal); Severe (child is ill and feeds poorly)
detects both viable and non-viable RSV. Test performance depends on the antigen load in the collected specimen and involves a rapid immunochromatographic analysis of the nasopharyngeal lavage. The overall sensitivity of the test is 70–93% while the specificity ranges from 89%–100% [Blyth et al., 2011]. All RSV positive cases were reported weekly to the study co-ordinator by the virology laboratory. STATISTICAL ANALYSIS Data were entered into a standard statistical program (SPSS, IBM, Version 19) and analyzed using descriptive statistics. Means, standard deviations (SDs), and percentage were used to analyze demographics and RST scores for all hospitalized patients based on severity. Chi-square and ANOVA were employed to compare the RSV clinical severity rating and the RST score. A P-value 0.05) and the largest percentage of infants (60%) hospitalized for RSV lower respiratory tract infection received a low-risk score on the RST and would not have qualified for prophylaxis (Table I). Of interest, the mean age of presentation with lower respiratory tract infection-related hospitalization was 7.4 months and the older age (6months) is in agreement with some population based studies reported in the literature [Nair et al., 2010; Houben et al., 2011; Sim~oes et al., 2011]. Several reasons may account for the results of this study. First, the sample size of the pilot project was
relatively small. However, similar findings were also documented by Paes et al. [2009] who found that the RST did not discriminate between low versus moderate to high-risk RSV-positive term infants who required hospitalization. In the current study, there was additionally a mismatch between the validated, clinical Kristjansson severity rating, and the robust RST model where infants with the mildest respiratory symptomatology had the highest mean scores (47). Second, it is likely that other risk factors as identified by Houben et al. [2011] may be more significant in the term population. Figueras-Aloy et al. [2004] noted that the risk factors for RSV hospitalization in a retrospective study (FLIP-1) involving 33–35 weeks’ gestational age infants did not concur with those found in a prospective study [Figueras-Aloy et al., 2008; FLIP-2] that enrolled infants who were 32–35 weeks. This was in part due to study design but the inclusion of one extra week (infants who were 32 weeks gestational age) in the latter study may have influenced the results. This supports the premise that risk factor models that have good predictive value for RSV-related hospitalization in a defined subset of preterm infants should not be loosely applied to others of varying gestational ages with the expectation of similar outcomes. Last, socio-economic status, country-specific epidemiological, and environmental risk factors not included in the Canadian risk scoring tool may have reduced the predictive power to detect RSV-related hospitalization [Sampalis et al., 2008]. In conclusion, the RST prove to have limited value in the prediction of RSV-related hospitalization in term infants, nor did it correlate with the clinical severity of illness. The absence of positive trends in the results indicates that a larger study based on a similar hypothesis, irrespective of the risk scoring model utilized, is likely to yield similar findings. Targeting approximately 8% of a universally large term birth cohort, which was reported by Houben et al. [2011] to be at highest risk for RSV lower respiratory tract infection for prophylaxis is also not J. Med. Virol. DOI 10.1002/jmv
1290
Mosalli et al.
cost-effective. Further studies are needed to consolidate a model that best predicts severe RSV disease in this population and subsequent hospitalization. REFERENCES Blanken MO, Koffijberg H, Nibbelke EE, Rovers MM, Bont L. Dutch RSV Neonatal Network. 2013. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: A multicenter birth cohort study. PLoS ONE 8:e59161. Blyth CC, Booy R, Dwyer DE. 2011. Point of care testing: Diagnosis outside the virology laboratory. Methods Mol Biol 665:415– 433. 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. Butt ML, Symington A, Janes M, Elliott L, Steele S, Paes BA. 2011. The impact of prophylaxis on paediatric intensive care unit admissions for RSV infection: A retrospective, single-centre study. Eur J Pediatr 170:907–913. Chin HJ, Seng QB. 2004. Reliability and validity of the respiratory score in the assessment of acute bronchiolitis. Malays J Med Sci 11:34–40. Feng L, Li Z, Zhao S, Nair H, Lai S, Xu W, Li M, Wu J, Ren L, Liu W, Yuan Z, Chen Y, Wang X, Zhao Z, Zhang H, Li F, Ye X, Li S, Feikin D, Yu H, Yang W. 2014. Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013. PLoS ONE 9:e99419. Figueras-Aloy J, Carbonell-Estrany X, Quero J. IRIS Study Group. 2004. Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33-35 weeks in Spain. Pediatr Infect Dis J 23:815–820. Figueras-Aloy J, Carbonell-Estrany X, Quero-Jim enez J, Fern andez-Colomer B, Guzm an-Caba~ nas J, Echaniz-Urcelay I. Domenech-Martnez E; IRIS Study Group. 2008. FLIP-2 Study: Risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks. Pediatr Infect Dis J 27:788– 793. Frogel M, Nerwen C, Cohen A, VanVeldhuisen P, Harrington M, Boron M. Palivizumab Outcomes Registry Group. 2008. Prevention of hospitalization due to respiratory syncytial virus: Results from the Palivizumab Outcomes Registry. J Perinatol 28:511– 517. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P. 2009. The burden of respiratory syncytial virus infection in young children. N Engl J Med 360:588–598. Hasegawa K, Mansbach JM, Teach SJ, Fisher ES, Hershey D, Koh JY, Clark S, Piedra PA, Sullivan AF, Camargo CA, Jr. 2014. Multicenter study of viral etiology and relapse in hospitalized children with bronchiolitis. Pediatr Infect Dis J 33:809– 813. € R, Ruuskanen Heikkinen T, Valkonen H, Lehtonen L, Vainionp€ aa O. 2005. Hospital admission of high risk infants for respiratory syncytial virus infection: Implications for palivizumab prophylaxis. Arch Dis Child Fetal Neonatal Ed 90:F64–F68. Horn SD, Smout RJ. 2003. Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr 143:S133–S141. Houben ML, Bont L, Wilbrink B, Belderbos ME, Kimpen JL, Visser GH, Rovers MM. 2011. Clinical prediction rule for RSV bronchiolitis in healthy newborns: prognostic birth cohort study. Pediatrics 127:35–41. Kristj ansson S, Lødrup Carlsen KC, Wennergren G, Strannega˚rd IL, Carlsen KH. 1993. Nebulised racemic adrenaline in the treatment of acute bronchiolitis in infants and toddlers. Arch Dis Child 69:650–654. Kusuda S, Takahashi N, Saitoh T, Terai M, Kaneda H, Kato Y, Ohashi A, Watabe S, Joh-o K, Hirai K. 2011. Survey of pediatric ward hospitalization due to respiratory syncytial virus infection after the introduction of palivizumab to high-risk infants in Japan. Pediatr Int 53:368–373.
J. Med. Virol. DOI 10.1002/jmv
Lanct^ ot KL, Masoud ST, Paes BA, Tarride JE, Chiu A, Hui C, Francis PL, Oh PI. 2008. The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32-35 weeks: A Canadian-based analysis. Curr Med Res Opin 24:3223–3237. Langley JM, Wang EE, Law BJ, Stephens D, Boucher FD, Dobson S, McDonald J, MacDonald NE, Mitchell I, Robinson JL. 1997. Economic evaluation of respiratory syncytial virus infection in Canadian children: a Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study. J Pediatr 131:113–117. Langley GF, Anderson LJ. 2011. Epidemiology and prevention of respiratory syncytial virus infections among infants and young children. Pediatr Infect Dis J 30:510–517. Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I, Sampalis J, Walti H, Robinson J, O’Brien K, Majaesic C, Caouette G, Frenette L, Le Saux N, Simmons B, Moisiuk S, Sankaran K, Ojah C, Singh AJ, Lebel MH, Bacheyie GS, Onyett H, Michaliszyn A, Manzi P, Parison D. 2004. The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J 23:806–814. Makari D, Hoopes JM, White N. 2009. Impact of RSV: Implications for managed care. Manag Care 18:2–7. Mansbach JM, Piedra PA, Teach SJ, Sullivan AF, Forgey T, Clark S, Espinola JA, Camargo CA, Jr. MARC-30 Investigators. 2012. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med 166:700–706. Miron D, Srugo I, Kra-Oz Z, Keness Y, Wolf D, Amirav I, Kassis I. 2010. Sole pathogen in acute bronchiolitis: Is there a role for other organisms apart from respiratory syncytial virus? Pediatr Infect Dis J 29:e7–e10. Moreno-Perez D, Calvo C. Five Study Group. 2014. Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study. Influenza Other Respir Viruses 8:209–216. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O’Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Sim~ oes EA, Rudan I, Weber MW, Campbell H. 2010. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 375: 1545–1555. Navas L, Wang E, de Carvalho V, Robinson J. 1992. Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. J Pediatr 121:348–354. Paes B, Cole M, Latchman A, Pinelli J. 2009. Predictive value of the respiratory syncytial virus risk-scoring tool in the term infant in Canada. Curr Med Res Opin 25:2191–2196. Paes BA, Mitchell I, Banerji A, Lanct^ot KL, Langley JM. 2011. A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice. Can Respir J 18:e10–e19. Paes B, Mitchell I, Li A, Harimoto T, Lanct^ ot KL. 2013. Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005-2012) compared to other international registries. Clin Dev Immunol 2013:917068. Prais D, Danino D, Schonfeld T, Amir J. 2005. Impact of palivizumab on admission to the ICU for respiratory syncytial virus bronchiolitis: A national survey. Chest 128:2765–2771. Rudan I, O’Brien KL, Nair H, Liu L, Theodoratou E, Qazi S, Luksic I, Fischer Walker CL, Black RE, Campbell H. Child Health Epidemiology Reference Group (CHERG). 2013. Epidemiology and etiology of childhood pneumonia in 2010: Estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Glob Health 3:010401. Sampalis JS, Langley J, Carbonell-Estrany X, Paes B, O’Brien K, Allen U, Mitchell I, Aloy JF, Pedraz C, Michaliszyn AF. 2008. Development and validation of a risk scoring tool to predict respiratory syncytial virus hospitalization in premature infants born at 33 through 35 completed weeks of gestation. Med Decis Making 28:471–480.
Predicting RSV Hospitalization in Term Infants Sim~oes EA, Carbonell-Estrany X, Fullarton JR, Liese JG, FiguerasAloy J, Doering G, Guzman J. European RSV Risk Factor Study Group. 2008. A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33-35 weeks of gestational age, based on data from the Spanish FLIP Study. Respir Res 9:78. Sim~ oes EA, Mutyara K, Soh S, Agustian D, Hibberd ML, Kartasasmita CB. 2011. The epidemiology of respiratory syncytial virus lower respiratory tract infections in children less than 5 years of age in Indonesia. Pediatr Infect Dis J 30:778–784.
1291 Sommer C, Resch B, Sim~ oes EA. 2011. Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J 5:144–154. Thorburn K. 2009. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child 94:99–103. Willson DF, Landrigan CP, Horn SD, Smout RJ. 2003. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 143:S142–S149.
J. Med. Virol. DOI 10.1002/jmv
