International Journal of Pediatrics 5 Table 4: Recommendations for palivizumab prophylaxis in children with CHD. (i) ≤24 months of age with hemodynamically signiﬁcant cyanotic CHD (a) Infants receiving medication to control congestive heart failure (b) Infants with moderate-to-sever pulmonary hypertension (c) Infants with cyanotic heart disease (ii) Initiate 15 mg/kg of palivizumab prophylaxis monthly during RSV season (typically November through March in North America) (iii) Give additional dose of palivizumab 15 mg/kg in patients who require cardiopulmonary bypass for a surgical procedure and will continue to need prophylaxis as soon as they are medically stable Source: [41]. globally, would lead to a diﬀerent conclusion regarding cost- eﬀectiveness than an infant where the RSV hospitalization rate is lower such as in Florida [49, 50]. In addition, how costs are assigned in economic modeling may have an impact on the cost-eﬀectiveness of palivizumab since lost productivity and the assumption that palivizumab can reduce health- care resource utilization for recurrent wheezing have been included in some analyses [51]. Although pediatric cardiologists from Europe have published similar recommendations as the AAP regarding indications for palivizumab prophylaxis [52], other countries like the UK and Switzerland have adopted a more strict policy regarding palivizumab and recommend its administration only to infants less than six months of age who have left- to-right shunt hemodynamically signiﬁcant congenital heart disease and/or pulmonary hypertension (UK), or who are <12 months of age and have additional risk factors like cyanotic CHD, pulmonary hypertension, or congestive heart failure (Switzerland) [53]. There has been robust discussion as to whether infection with RSV or other viruses in infancy can lead to the development of asthma since previous studies have reported that persistent respiratory symptoms and impaired lung function can occur until later childhood and even young adulthood [54, 55]. Whether viral respiratory tract infections are causal factors of asthma or merely are coincidental in a child predisposed to asthma is still unresolved [56]. Recently, a multicenter trial in Europe and Canada demonstrated that palivizumab administration given in the ﬁrst year of life to premature infants signiﬁcantly decreased the likelihood of recurrent wheezing in children up to 5 years of age but did not have any eﬀect on infants who had family history of atopy, suggesting that the cause of wheezing is diﬀerent between asthma and RSV [57]. The debate about the cost-eﬀectiveness about palivi- zumab only serves to highlight the need for more eﬀective prevention strategies for such a prominent illness that contributes signiﬁcantly to worldwide childhood morbidity and mortality. 4. Future Directions Previous attempts at developing a vaccine to prevent RSV infection have been unsuccessful due to several factors such as the early age of infection, the ability of the virus to evade preexisting immune responses, a failure of natural infection to confer immunity throughout an individual’s life, a legacy of vaccine-enhanced disease, and animal models that do not precisely mimic human RSV [58]. In the 1960s, recipients of a formalin-inactivated vaccine experienced increased morbidity and mortality upon subsequent exposure to RSV [59, 60]. Since this time, subunit vaccines that target the F and G proteins of RSV, the delivery of vaccine antigens by live viral vectors such as recombinant attenuated parainﬂuenza virus type-3 expressing RSV-F protein, and live-attenuated vaccines have undergone testing in preclinical trials and Phase I trials and may hold promise as future vaccine candidates against RSV [58, 61, 62]. Inducing neutralizing antibody to reduce antigen accumulation and inducing CD8+ T cells to clear RSV-infected cells are thought to be important principles for RSV vaccine development [58]. However, even if a vaccine emerges, it is likely that multiple doses will be needed at frequent intervals so that adequate immunity against RSV develops. This may complicate eﬀorts to achieve the full beneﬁts of vaccination in low-income countries where the burden of RSV is greatest. Additionally, a small interfering RNA (siRNA) that impacts RSV replication, including RNA polymerase function, was delivered via nasal spray to 88 subjects before and after they were given an inoculum of wild-type RSV and signiﬁcant antiviral activity with favorable safety proﬁle was demonstrated supporting further investigation of this approach as a treatment for RSV infection [63]. This research may also lead to the development of other locally delivered siRNAs against other respiratory pathogens. References [1] R. R. Thiagarajan and P. C. Laussen, “Mortality as an outcome measure following cardiac surgery for congenital heart disease in the current era,” Paediatric Anaesthesia, vol. 21, no. 5, pp. 604–608, 2011. [2] G. D. Webb, “Care of adults with congenital heart disease—a challenge for the new millennium,” Thoracic and Cardiovascu- lar Surgeon, vol. 49, no. 1, pp. 30–34, 2001. [3] O. Loup, C. von Weissenﬂuh, B. Gahl, M. Schwerzmann, T. Carrel, and A. Kadner, “Quality of life of grown-up congenital heart disease patients after congenital cardiac surgery,” European Journal of Cardio-Thoracic Surgery, vol. 36, no. 1, pp. 105–111, 2009. [4] L. F. Eskedal, P. S. Hagemo, A. Eskild, K. F. Frøslie, S. Seiler, and E. Thaulow, “A population-based study relevant to seasonal