Respiratory syncytial virus, infants and intensive therapy

Bueno, Ieda Aparecida Correa; Riccetto, Adriana Gut Lopes; Morcillo, André Moreno; Arns, Clarice Weis; Baracat, Emílio Carlos Elias

doi:10.1590/S1413-86702012000100016

Abstract

The aims of this study were to determine the presence of respiratory syncytial virus (RSV) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (PICU) of two university teaching hospitals in São Paulo State, Brazil. Nasopharyngeal secretions were tested for the RSV by the polymerase chain reaction. Positive and negative groups for the virus were compared in terms of evolution under intensive care (mechanical pulmonary ventilation, medications, invasive procedures, complications and case fatality). Statistical analysis was performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients were previously healthy while 85.7% required mechanical pulmonary ventilation, 20/21 patients presented with at least one complication, and the fatality rate was 14.3%. RSV positive and negative groups did not differ for the variables studied. Patients involved in this study were critically ill and needed multiple PICU resources, independently of the presence of RSV. Further studies involving larger cohorts are needed to assess the magnitude of the impact of RSV on the clinical evolution of infants admitted to the PICU in our settings.

Respiratory syncytial virus; Infants; Intensive therapy; Genotypes

BRIEF COMMUNICATION

Respiratory syncytial virus, infants and intensive therapy

Ieda Aparecida Correa Bueno^I; Adriana Gut Lopes Riccetto^I,^*; André Moreno Morcillo^I; Clarice Weis Arns^II; Emílio Carlos Elias Baracat^I

^IDepartment of Pediatrics, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil

^IIVirology Laboratory, Department of Genetics, Evolution and Bioagents, Institute of Biology, Universidade Estadual de Campinas, SP, Brazil

ABSTRACT

The aims of this study were to determine the presence of respiratory syncytial virus (RSV) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (PICU) of two university teaching hospitals in São Paulo State, Brazil. Nasopharyngeal secretions were tested for the RSV by the polymerase chain reaction. Positive and negative groups for the virus were compared in terms of evolution under intensive care (mechanical pulmonary ventilation, medications, invasive procedures, complications and case fatality). Statistical analysis was performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients were previously healthy while 85.7% required mechanical pulmonary ventilation, 20/21 patients presented with at least one complication, and the fatality rate was 14.3%. RSV positive and negative groups did not differ for the variables studied. Patients involved in this study were critically ill and needed multiple PICU resources, independently of the presence of RSV. Further studies involving larger cohorts are needed to assess the magnitude of the impact of RSV on the clinical evolution of infants admitted to the PICU in our settings.

Keywords: Respiratory syncytial virus; Infants; Intensive therapy; Genotypes

Respiratory syncytial virus (RSV) leads to acute lower respiratory tract infection (ALRTI) in approximately 10% of infant cases^1,2 and requires mechanical pulmonary ventilation (MPV) in 7% to 21% of hospitalized patients.^3,4 A review of recent articles retrieved from the Medline database using the search words "Respiratory Syncytial Virus Intensive Therapy Infants" involving different study cohorts showed that newborns and young infants with RSV are at greater risk for MPV, longer hospital stay and higher incidence of complications.^5-14 Although the presence of comorbidities (pneumonia, cardiopathy and prematurity) is associated to poorer evolution, many ICU patients were previously healthy.^5-10 The aims of this study was to determine the presence of RSV and the clinical features of this infection in infants with ALRTI hospitalized in the pediatric intensive care unit (PICU). A prospective descriptive and analytical study was conducted in infants aged between zero and 12 months with ALRTI hospitalized in the PICU of two University teaching hospitals in the Campinas region of São Paulo state, Brazil in 2004, 2007 and 2008. Collection was performed between the months of April and September, a period previously reported to be associated with the highest incidence of the virus in the region.^4,15

The inclusion criteria were infants between 0 and 12 months of life and hospitalized in the PICU due to ALRTI. The sole criterion for exclusion was onset of symptoms more than seven days prior to admission.

The diagnosis of ALRTI was reached based on clinical criteria (fever, cough, tachypnea, rales or wheezes on auscultation), supplemented by radiological (hyperinflation, opacities) and gasometric (hypoxemia, hypercapnia, respiratory acidosis) criteria. The combination of these findings determined the need for MPV or otherwise in these patients according to specific medical protocols.^16,17Nasopharyngeal secretions were collected by aspiration from all patients during the first three days of admission. The material obtained was analyzed by the polymerase chain reaction (PCR) molecular method.¹⁸ Patients were divided into RSV positive and RSV negative groups and assessed for gender, age on admission, previous diseases, length of PICU stay, need for/time on MPV, use of medications, and invasive procedures. During the PICU stay, patients were assessed for prognostic factors of worse evolution on MPV by calculating the ventilation index (VI = peak inspiratory pressure x mechanical respiratory rate/1000) and partial oxygen pressure/fraction of inspired oxygen (PaO₂/FIO₂), and by examining the worse gasometry value of the first day of MPV.¹⁹ Complications were registered after the first day of ICU stay and grouped into cardiologic (myocarditis with cardiac insufficiency or arrhythmias), renal (acute renal insufficiency), neurologic (encephalitis with convulsions and coma), hydroelectrolytic (acidosis, sodium potassium, calcium disturbances), hematologic (anemia, leukopenia, plateletopenia) and respiratory (atelectasis, pleural stroke, pneumothorax) problems.

Data were stored using the Excel program and analysis performed by version 8.2 of the SAS (Statistical Analysis System) software (SAS Institute INC, 1999-2001, Cary, NC, USA). The Mann Whitney and Fisher's exact tests were employed for statistical analysis adopting a significance level of 0.05.

A signed term of informed consent was provided by the guardians of all patients. This project was previously approved by the Research Ethics Committee of the School of Medical Sciences of the Universidade Estadual de Campinas (UNICAMP) under process number 076/2003 and was conducted in accordance with the ethical principles of the World Medical Association and Declaration of Helsinki.

Results given are based on the analysis of 21 infants aged between zero and 12 months hospitalized in the PICU for ALRTI. Regarding patient profile, median age was 2.4 months, 12 subjects were male (52.2%) and eight (38.1%) tested positive on PCR for RSV. Comparison of the RSV-positive and RSV-negative groups by the Mann-Whitney test revealed no difference in the variables age on admission (p = 0.601) or length of PICU stay (p = 0.133). The majority of patients were previously healthy (57.1%) whereas 9/21 (42.9%) had previous diseases (acquired immunodeficiency, genetic syndromes, cardiopathies). Similarly, the two groups did not differ for previous diseases (p = 0.200). A total of 18/21 (85.7%) patients required mechanical pulmonary ventilation during the PICU stay. No difference between the study groups was found for time on ventilatory support (p = 0.762, Fisher's exact test), and ventilation index (p = 0.427, Mann- Whitney test) or PaO₂/FiO₂ (p = 0.384, Mann-Whitney Test). With regard to medication use during PICU stay, no difference was found in use of endovenous corticosteroids, different types of antibiotics, vasoactive drugs or continuous sedation with benzodiazepines or opioids (p > 0.05). The patients were underwent a variety of invasive procedures: venous catheter insertion (by deep venipuncture/Intracath^®, percutaneous puncture/PICC^® and vein dissection/phlebotomy); use of vesical relief and delay probe; chest drainage. In terms of frequency of these procedures, a significant difference was found between groups only for the phlebotomy procedure which was more frequent in RSV-positive patients (p = 0.042).

During the PICU stay, 20/21 patients had complications, predominantly respiratory problems (15/21; 71.4%) although no difference between RSV-positive and RSV-negative groups was evident (Table 1). Concerning fatalities, one death occurred in the RSV-positive group and two deaths in the RSV-negative group (3/21, 14.3%), a non-significant difference between the groups (p = 0.510, Fisher's exact test). The deaths occurred in young infants that evolved clinically with cardiovascular and infectious complication, one of whom had Down's syndrome. Patient characteristics are shown in Table 2.

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The overall result of the present study was that clinical pictures among the cohort studied were no more severe in RSV-positive patients than RSV-negative individuals. In the present population, although the proportion of males and the age group were consistent with those of a similar study,¹⁵ RSV-positive and negative patients were comparable in terms of PICU stay, MPV and complications, a finding that contrasts with earlier reports.^6,8,11,14However, it should be noted that the present study included infants only up to 12 months of age and that the worse evolution seen in RSV-positive patients affected mainly young infants, particularly newborns.^5,8 Another noteworthy point is that comparison of our results with those in the literature was hampered by the fact that the present study included three forms of clinical presentation (bronchiolitis, pneumonia and pneumonia plus bronchiolitis) whereas the majority of earlier studies considered only patients with bronchiolitis.^1,2,16 This broader inclusion was based on results of a previous study involving a large cohort (n = 144) performed in the same hospitals that showed a predominance of the bronchiolitis-plus-pneumonia form among patients hospitalized for RSV.²⁰ Akin to the findings of other authors,¹⁰ the present cohort comprised patients that were predominantly previously healthy (57.1%). In contrast to other cohorts investigated, the patients with previous diseases in the present study did not have worse evolution.^6,8,11,14 This finding might be explained by the small number of patients included in the study.

In the present study sample patients were critically ill and needed multiple PICU resources, independently of the presence of RSV.

Acknowledgements

This study received financial support from Fundo de Auxílio à Pesquisa (FAEP) of the Universidade Estadual de Campinas (UNICAMP), Brazil.

Conflict of interest

All the authors declare to have no conflict of interest.

Received 18 August 2011

Accepted 19 September 2011

References

1. Shay DK, Holman RC, Newman D, et al. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. 1999;282:1440-6.
2. Denny FW. Acute respiratory infections in children: etiology and epidemiology (review). Pediatr Rev. 1987;9:135-46
3. Prodhan P, Sharoor-Karni S, Lin J, et al. Predictors of respiratory failure among previously healthy children with respiratory syncytial virus infection. Am J Emerg Med. 2011;29(2):168-73.
4. Riccetto AGL, Ribeiro JD, Silva MTN, et al. Respiratory Syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks. Braz J Infect Dis. 2006;10(5);357-61.
5. Oñoro G, Pérez Suárez E, Iglesias Bouzas MI, et al. Severe bronchiolitis. Changes in epidemiology and respiratory support. An Pediatr (Barc). 2011;74(6):371-6.
6. García CG, Bhore R, Soriano-Fallas A, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010;126(6):e1453-60.
7. Welliver RC Sr, Checchia PA, Bauman JH, et al. Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children. Curr Med Res Opin. 2010;26(9):2175-81.
8. Forbes ML, Hall CB, Jackson A, et al. Comparative costs of hospitalisation among infants at high risk for respiratory syncytial virus lower respiratory tract infection during the first year of life. J Med Econ. 2010;13(1):136-41.
9. Levin D, Tribuzio M, Green-Wrzesinki T, et al. Empiric antibiotics are justified for infants with respiratory syncytial virus lower respiratory tract infection presenting with respiratory failure: a prospective study and evidence review. Pediatr Crit Care Med. 2010;11(3):390-5.
10. Berger TM, Aebi C, Duppenthaler A, et al. Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005).Infection. 2009;37(2):109-16.
11. Vieira RA, Diniz EM, Ceccon ME. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity. J Bras Pneumol. 2010;36(1):59-66.
12. Straliotto SM, Siqueira MM, Machado V, et al. Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects Mem Inst Oswaldo Cruz. 2004;99(8):883-7.
13. Diniz EM, Vieira RA, Ceccon ME, et al. Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation. Rev Inst Med Trop São Paulo. 2005;47(1):37-44.
14. Vieira RA, Diniz EM, Vaz FA. Clinical and laboratory study of newborns with lower respiratory tract infection due to respiratory viruses. J Matern Fetal Neonatal Med. 2003;13(5):341-50.
15. Cintra OAL, Owa MA, Machado AA, et al. Occurrence and severity of infections caused by subgroup A and B respiratory syncytial virus in children in southeast Brazil. J Med Virol. 2001;65:408-12.
16. American Academy of Pediatrics Sub-committee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774-93.
17. Almeida-Junior AA, Lima AES. Insuficiência Respiratória. In: Lopes CE, Brandão MB, Vilela R, Eds. Terapia Intensiva em Pediatria. São Paulo, Editora Sarvier, 2010.pp 3-20.
18. da Silva LH, Spilki FR, Riccetto AG, et al. Genetic variability in the G protein gene of human respiratory syncytial virus isolated from the Campinas metropolitan region, Brazil. J Med Virol. 2008;80(9):1653-60.
19. Almeida-Júnior AA, da Silva MT, Almeida CC, et al. Association between ventilation index and time on mechanical ventilation in infants with acute viral bronchiolitis. J Pediatr (Rio J). 2005;81(6):466-70.
20. Riccetto AG, Silva LH, Spilki FR, et al. Genotypes and clinical data of respiratory syncytial virus and metapneumovirus in Brazilian infants: a new perspective. Braz J Infect Dis. 2009;13(1):35-9.

*

Corresponding author at: Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, Barão Geraldo, 13083-970, São Paulo, SP, Brazil. E-mail address:

aglriccetto@gmail.com (Adriana Gut Lopes Riccetto)

Publication Dates

Publication in this collection
16 Feb 2012
Date of issue
Feb 2012

History

Received
18 Aug 2011
Accepted
19 Sept 2011

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

[1] 1. Shay DK, Holman RC, Newman D, et al. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. 1999;282:1440-6.

[2] 2. Denny FW. Acute respiratory infections in children: etiology and epidemiology (review). Pediatr Rev. 1987;9:135-46

[3] 3. Prodhan P, Sharoor-Karni S, Lin J, et al. Predictors of respiratory failure among previously healthy children with respiratory syncytial virus infection. Am J Emerg Med. 2011;29(2):168-73.

[4] 4. Riccetto AGL, Ribeiro JD, Silva MTN, et al. Respiratory Syncytial virus (RSV) in infants hospitalized for acute lower respiratory tract disease: incidence and associated risks. Braz J Infect Dis. 2006;10(5);357-61.

[5] 5. Oñoro G, Pérez Suárez E, Iglesias Bouzas MI, et al. Severe bronchiolitis. Changes in epidemiology and respiratory support. An Pediatr (Barc). 2011;74(6):371-6.

[6] 6. García CG, Bhore R, Soriano-Fallas A, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010;126(6):e1453-60.

[7] 7. Welliver RC Sr, Checchia PA, Bauman JH, et al. Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children. Curr Med Res Opin. 2010;26(9):2175-81.

[8] 8. Forbes ML, Hall CB, Jackson A, et al. Comparative costs of hospitalisation among infants at high risk for respiratory syncytial virus lower respiratory tract infection during the first year of life. J Med Econ. 2010;13(1):136-41.

[9] 9. Levin D, Tribuzio M, Green-Wrzesinki T, et al. Empiric antibiotics are justified for infants with respiratory syncytial virus lower respiratory tract infection presenting with respiratory failure: a prospective study and evidence review. Pediatr Crit Care Med. 2010;11(3):390-5.

[10] 10. Berger TM, Aebi C, Duppenthaler A, et al. Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005).Infection. 2009;37(2):109-16.

[11] 11. Vieira RA, Diniz EM, Ceccon ME. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity. J Bras Pneumol. 2010;36(1):59-66.

[12] 12. Straliotto SM, Siqueira MM, Machado V, et al. Respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects Mem Inst Oswaldo Cruz. 2004;99(8):883-7.

[13] 13. Diniz EM, Vieira RA, Ceccon ME, et al. Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation. Rev Inst Med Trop São Paulo. 2005;47(1):37-44.

[14] 14. Vieira RA, Diniz EM, Vaz FA. Clinical and laboratory study of newborns with lower respiratory tract infection due to respiratory viruses. J Matern Fetal Neonatal Med. 2003;13(5):341-50.

[15] 15. Cintra OAL, Owa MA, Machado AA, et al. Occurrence and severity of infections caused by subgroup A and B respiratory syncytial virus in children in southeast Brazil. J Med Virol. 2001;65:408-12.

[16] 16. American Academy of Pediatrics Sub-committee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006;118:1774-93.

[17] 17. Almeida-Junior AA, Lima AES. Insuficiência Respiratória. In: Lopes CE, Brandão MB, Vilela R, Eds. Terapia Intensiva em Pediatria. São Paulo, Editora Sarvier, 2010.pp 3-20.

[18] 18. da Silva LH, Spilki FR, Riccetto AG, et al. Genetic variability in the G protein gene of human respiratory syncytial virus isolated from the Campinas metropolitan region, Brazil. J Med Virol. 2008;80(9):1653-60.

[19] 19. Almeida-Júnior AA, da Silva MT, Almeida CC, et al. Association between ventilation index and time on mechanical ventilation in infants with acute viral bronchiolitis. J Pediatr (Rio J). 2005;81(6):466-70.

[20] 20. Riccetto AG, Silva LH, Spilki FR, et al. Genotypes and clinical data of respiratory syncytial virus and metapneumovirus in Brazilian infants: a new perspective. Braz J Infect Dis. 2009;13(1):35-9.