Aims: To determine the number of infants in the Mersey and North West regions with congenital cardiac disease for whom palivizumab may be appropriate, and to examine the potential impact of introducing prophylaxis with palivizumab on these patients and their economic management. Methods: We identified those infants deemed to be at high risk, matching the population recently studied by the Cardiac Synagis Group, from the database of the cardiology department of the hospital. The number of patients under the care of the paediatric cardiologists admitted to Alder Hey Hospital with respiratory syncytial viral bronchiolitis over the last three seasons was identified from hospital coding records, and the database of the cardiology department. Results: There are 131 patients at high risk each year. Of these, over the last three “bronchiolitis seasons”, 39 infants have been admitted to the hospital with bronchiolitis due to the respiratory syncytial virus. This represents a hospitalisation rate of 10 per cent, as was seen in the study of the Cardiac Synagis Group. Using a monthly dose of 15 milligrams per kilogram for five doses, the cost per patient is 2,650 pounds sterling for the season. To treat the 131 patients seen at Alder Hey, therefore, would cost 346,800 pounds each year. Applying the reductions in hospitalisation identified in the study by the Cardiac Synagis Group to our population would produce an expected reduction in patients hospitalised from 13 to 7 per year, reducing the total length of stay in our hospital wards from 169 to 76 days, and in the paediatric intensive care unit from 93 to 21 days. This amounts to a potential saving of 190,800 pounds per year. Reducing transfers to more distant paediatric intensive care units for referrals refused because of lack of beds could save an additional 50,000 pounds. Discussion: We estimate the net cost of introducing palivizumab for this population to be 106,000 pounds per year. There would, of course, be additional costs involved in setting up this service, as well as additional savings and benefits. This cost is comparable with other new biologic therapies now routinely used in the United Kingdom, such as etanercept for juvenile arthritis. There are, currently, no other obvious therapies that have the potential to reduce admissions to hospital and intensive care during the winter months, when beds are at their most scarce.

A recent, randomised, double-blind, placebo-controlled trial has demonstrated the effectiveness of palivizumab (Synagis®) for prophylaxis against infection by the respiratory syncytial virus in 1,287 young children with congenital cardiac disease. Guidelines for the use of palivizumab in these children considered to be at high risk were published by the American Academy of Pediatrics, followed by similar guidelines from the British Paediatric Cardiac Association, and recommendations from a number of other individual countries, including Canada, Germany, Spain, and France.

In May, 2004, further discussion was held between a group of 15 paediatric cardiologists at a European forum for clinical management held in Munich, Germany. The objective of this forum was to define optimal recommendations on prevention of infection by the respiratory syncytial virus in infants and young children with congenital cardiac disease, appropriate to the clinical needs and style of those practising in paediatrics in individual countries. Participants were invited because of their knowledge of the therapeutic area, and for their experience of using palivizumab for prophylaxis against the respiratory syncytial virus in children with congenitally malformed hearts. Measures to educate the carers of children with such congenital malformations on precautions against infection by the respiratory syncytial virus were discussed, along with the many different aspects of best practice for therapeutic prophylaxis with palivizumab. The most appropriate timing of prophylaxis, recommendations for which children are most likely to benefit from prophylaxis, and suggested protocols were among the issues covered. The recommendations resulting from the discussions are presented in this paper, as a step towards reaching consensus.

The respiratory syncytial virus is the most common cause of infection of the lower respiratory tract in infants and young children, and is the leading cause of hospitalisation and death due to viral illness during the first year of life. In otherwise healthy infants, the virus usually causes only mild respiratory illness, but premature babies and infants with chronic lung disease, those with congenitally malformed hearts, or those who are immunodeficient, are at increased risk of serious illness, hospitalisation, and death. Recent infection with the virus is also associated with increased postoperative complications after corrective surgery for congenitally malformed hearts. No effective vaccine is currently available, and treatment is limited to supportive therapy. Prevention in groups deemed to be at high-risk, therefore, is essential. In addition to measures for control of infection, prophylactic immunotherapy is indicated in selected patients. Palivizumab (Synagis®) is a monoclonal antibody indicated for the prevention of serious viral disease of the lower respiratory tract in premature infants, those with chronic lung disease, and those with haemodynamically significant congenital cardiac lesions. Palivizumab is given intramuscularly, usually as a monthly injection during the so-called “season”. In a recent international, randomised, double-blind, placebo-controlled trial in 1,287 children less than or equal to 2 years old with haemodynamically significant congenital cardiac malformations, prophylaxis achieved a relative reduction of 45 per cent in the incidence of antigen-confirmed viral-related hospitalisation, and reduced the duration of hospital stay by 56 per cent. National and international guidelines, therefore, now recommend routine prophylaxis in the first year of life in children with haemodynamically significant congenital cardiac disease.

All newborn infants have limited pulmonary reserve compared with older children. This puts them at increased risk of respiratory complications, such as those associated with infection by the respiratory syncytial virus. Young children with congenital cardiac disease are particularly likely to suffer severe disease related to infection by the virus. In these children, the extreme vulnerability of the lung to pulmonary oedema is compounded by the additional burden caused by the respiratory syncytial virus.

In addition to the well-documented acute pulmonary effects of infection with the respiratory syncytial virus, there may also be consequent long-term respiratory morbidity. Clinical studies have shown that infection by the virus in infancy is associated with a higher risk of developing subsequent bronchial obstructive disease. Much debate surrounds the mechanisms underlying this association. It is thought that a combined immunological and neurogenic response mechanism is likely. Prevention of severe respiratory disease in infants and young children with congenital heart disease due to infection by the virus may, therefore, offer both immediate and long-term benefits. Indeed, an increasing body of evidence supports this hypothesis, indicating a clinical rationale for prophylaxis against the virus in infancy, in order to reduce the chance of developing reactive airways disease and asthma in later life.