194 JW Jung • RSV infection in children with congenital heart disease Global Trends of Respiratory Syncytial virus infection with congenital heart diseases The development of the recent innovative interventions is expected to change RSV infection treatment in infants with CHD. Earlier studies in RSV infection on CHD patients revealed that lower respiratory infection by RSV was potentially lethal leading to increased mortality and morbidity in HS-CHD infants1-6,12). On the effects of RSV infection during late 1970’s in infants with CHD reported in 1982, the severity of RSV bronchiolitis in children with CHD for a hospital based cohort study of all infants (n=699) was significantly greater than those without CHD, categorized by those who require intensive care (63% vs. 14%,P<0.001) and assisted ventilation (22% vs. 5%,P <0.01). These fatality rate was higher in the CHD group (37% vs. 1.5%,P<0.01). In infants with RSV and pulmonary hypertension, the mortality rate was extraordinarily high (73%)4). In these subgroup, nosocomial infection was associated with mortality rate, compared with children without CHD (44% vs. 5%)4). A review in Canada between 1988 and 1991 was evaluated for 260 children with CHD, hospitalized with RSV disease at 12 pediatric tertiary care centers, and 87 (33%) required intensive care and 49 (19%) required mechanical ventilation13). Other reports released in 1992 and 1995 revealed that pulmonary hypertension in particular was the single most important factor in causing severe RSV infection in infants with CHD14). The morbidity caused by RSV infection in children with CHD correlates with the severity of the underlying cardiac disease, represented by the degree of compromise of the baseline functional status in cardio-pulmonary system, pulmonary flow/ventilation mechanics, degree of cyanosis, level of pulmonary hypertension and extent of ventilation/perfusion mismatch14,15). In 1990 through 1995, a retrospective review for 25 infants with CHD showed that RSV bronchiolitis and pneumonia causes substantial morbidity and even mortality in the immediate period surrounding either palliative or corrective cardiac surgery15). Car- diac surgery performed during symptomatic RSV bronchiolitis and pneumonia is associated with a high risk of postoperative complications. In particular, postoperative pulmonary hypertension can cause immediate postoperative mortality. These complications in CHD patients appeared to occur more frequently and sometimes fatal in patients who had undertaken earlier surgery, while bronc- hiolitis due to RSV infection continues as compared with those who had later surgery. Therefore, to obtain complete and safe results after congenital heart surgery, procedures should not be performed in an infant who has not fully recovered from an acute RSV infection. In addition, RSV is also an important cause of postoperative nosocomial infection. It may be due to a transient immunologic dysfunction following cardiopulmonary bypass and a possibility for dilution of serum neutralizing antibodies. Preoperative screening for asymptomatic RSV infection has been suggested as a main key to reduce this morbidity. This was the basic idea in the development of RSV vaccination, to prevent severe RSV infection in high-risk infants 12,14,15). For recent 10 years with advances in intensive care, mortality rates in CHD patients combined with RSV has decreased to below 2% of the population11,12). Nevertheless the requirements of intensive care for CHD patients with RSV infection in progress, were much higher as almost 2.5 times compared with those without current RSV infection, and as up to 1.7 times than those for non-CHD children with RSV infection. The need of mechanical ventilation for RSV infection in CHD patients was recognized as about 2.4 times higher than in non-CHD patients1,4-6,12). This infection is further threatening to particular conditions of CHD patients: infants with congestive heart failure, cyanosis, or pulmonary hypertension. Under these cardiac conditions there are severely restricted capacity of cardiac function to increase cardiac output and oxygen delivery. As RSV pneumonitis progresses in those infants with compromised cardiac performance, oxygen uptake was markedly impaired and the work of breathing was gradually increased5,14,15). Non-sustained immunity and difficulties to develop the effective vaccines made RSV management directed toward a passive im- munotherapy for these high risk children16-18). Palivizumab is one of the first humanized murine monoclonal antibody targeting the RSV envelope F glycoprotein, and in a Phase III clinical trial palivizumab through randomized double-blind study of 1,287 patients from 1998, significantly reduced RSV hospitalization in children with HS-CHD safely8). Study results showed a 45% relative reduction in RSV hospitalization among children receiving palivizumab prophylaxis (9.7% vs. 5.3%, P =0.003). Other information was that serum palivizumab levels were reduced to 58% after cardiopulmonary bypass due to diluted effect. The American Academy of Pediatrics (AAP) revised its indications for palivizumab to include less than 24 month aged children with HS-CHD in 200319). In addition, the AAP recommended redosing of CHD patients following cardiopulmonary bypass to reach adequate serum concentration of neutralizing antibody to protect the vulnerable postoperative infant. Many countries including Japan have followed their own guidelines that identify high-risk patients and define the appropriate timing of vaccination, usually 5 doses during winter19-23). Its guidelines for CHD patients in Japan were approved for children less than 24 month of age at the start of RSV season in October 2005