Use of palivizumab and infection control measures to control an outbreak of respiratory syncytial virus in a neonatal intensive care unit confirmed by real-time polymerase chain reaction

Summary

Respiratory syncytial virus (RSV) is a potentially life-threatening infection in premature infants. We report an outbreak involving four infants in the neonatal intensive care unit (NICU) of our hospital that occurred in February 2010. RSV A infection was confirmed by real-time polymerase chain reaction. Palivizumab was administered to all infants in the NICU. There were no additional symptomatic cases and repeat RSV surveillance confirmed that there was no further cross-transmission within the unit. The outbreak highlighted the infection control challenge of very high bed occupancy in the unit and the usefulness of molecular methods in facilitating detection and management.

Introduction

Respiratory syncytial virus (RSV) is a cause of acute respiratory tract infection in persons of all ages and is the most common cause of lower respiratory tract infection in children aged <1 year.¹ By the age of 2 years, almost all children have been infected, and reinfection is a common occurrence.² RSV transmission occurs by inoculation of nasopharyngeal or ocular mucous membranes after contact with fomites or secretions containing RSV.3, 4 The most common route of transmission is direct contact, but droplets have also been implicated.⁵ RSV causes seasonal outbreaks worldwide. In the UK (Health Protection Agency, Colindale Surveillance of Influenza Group, London) and Ireland (Health Protection Surveillance Centre), peak numbers are reported every winter in December and January. Patients at risk for serious RSV infection include infants aged <6 months, infants born before 35 weeks of gestation and infants and children with underlying lung disease or congenital heart disease.⁶

RSV infection is potentially life-threatening in infants, particularly in premature infants, and it has caused serious outbreaks of infection in neonatal intensive care units (NICUs).7, 8, 9, 10, 11, 12 NICU outbreaks can lead to severe morbidity and mortality in preterm infants and incur very substantial financial costs.7, 8, 9, 10, 11, 12, 13, 14 One report of an outbreak of RSV at a NICU in the USA estimated costs of the outbreak at more than US$1 million.¹⁵

Palivizumab, a humanised monoclonal antibody directed against the RSV F glycoprotein, is recommended as prophylaxis for certain patient groups at risk of severe RSV infection. A large randomised multicentre controlled trial showed that palivizumab reduced hospitalisation due to RSV infection by 55% in such infants.¹⁶ More recently, motavizumab, an affinity-matured humanised monoclonal antibody against RSV has been developed, but its clinical utility is not yet defined.¹⁷

We have identified four reports in the literature on the use of palivizumab in NICU outbreaks.7, 9, 10, 12 Cox et al. described an outbreak of RSV in an 18-bedded unit which affected seven preterm infants and where palivizumab was offered to eight other babies in the unit.⁷ The authors felt that it was appropriate to offer protection from hospital-acquired RSV after three apparent separate transmission incidents had occurred despite heightened infection control measures on the unit. No further cases of RSV occurred (Figure 1).

Kilani et al. recommended palivizumab prophylaxis for all preterm infants in a NICU when an index case has been identified.⁸ Abadesso et al. described two separate RSV outbreaks in a large 26-bedded NICU where standard infection control measures were effective in the first outbreak (three cases), but not in the second outbreak.⁹ Palivizumab was given to all infants in the NICU after identification of the fifth case. There were no further cases of RSV and palivizumab was well tolerated. The authors concluded that palivizumab might be an adjunctive resource for the containment of severe RSV outbreaks. Kurz et al. found that palivizumab combined with conventional infection control measures aborted the spread of RSV in their NICU.10, 11 Despite the reported apparent benefit of this high cost intervention, the effectiveness of palivizumab prophylaxis in this setting has not been formally evaluated.⁹

We describe an outbreak of RSV involving four infants in the NICU of our hospital that occurred in February 2010. We report the role of a real-time PCR assay in confirmation of the outbreak and describe the measures, including prophylactic administration of palivizumab, taken to control the outbreak.