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Future directions in vaccine prevention of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the principal pathogen associated with lower respiratory tract illness (LRTI) in infants and children in the United States and in other industrialized nations. Approximately 80% of the children hospitalized for RSV disease are 1 year of age. From 1980 to 1996 bronchiolitis hospitalization rates in the United States in children 1 year of age increased substantially from 1.2 per 100 in 1980 to 3.1 per 100 in 1996. Estimated annual bronchiolitis hospitalization attributed to RSV ranges from 51 000 to 82 000 in children 12 months of age and 62 000 to 100 000 in children younger than 5 years of age. An additional 11 000 to 15 000 children 1 year of age in one study and 22 000 to 44 000 in another study are admitted annually for RSV pneumonia. 6 With advances in the care of critically ill children, the mortality attributed to pneumonia has decreased markedly. Similarly mortality attributed to RSV appears to have decreased to an estimated 500 deaths per year in infants. A decrease in mortality is well-documented for RSV-infected infants with complex congenital heart disease. 10 Despite the fact that the mortality rate in the United States has decreased, the severity of illness appears to have become greater in recent years; the proportion of infants requiring intubation and ventilatory assistance increased from 1.0% through 1993 to 1.7% from 1994 through 1996. Increasing illness severity has resulted in higher costs for hospitalizations; costs for infants with underlying cardiac disease averaged $26 230, and for those requiring ventilatory assistance the range was $60 320 to $246 630. 11 The economic burden to society is considerable with an estimated annual direct cost of $300 000 000 only for RSV pneumonia hospitalization. Worldwide acute respiratory illness (ARI) is responsible for an estimated 4 million deaths annually in children 5 years of age and is the leading contributor to the global burden of disease. In developing countries ARI is the leading cause of morbidity and mortality in infants and young children. Viruses are the pathogens most commonly recovered from children with LRTI, and RSV is the viral agent identified most frequently in children with LRTI. Well-defined seasonal patterns of RSV associated with outbreaks of bronchiolitis have been reported for many nonindustrialized countries. Mortality attributed to RSV may be significantly greater in nonindustrialized nations as noted by the frequent detection of RSV in young children who died of pneumonia. A license vaccine for the prevention of RSV is currently not available. Considerable progress, however, has been made in the development and evaluation of subunit and live attenuated candidate vaccines against RSV. Both major groups of vaccines offer advantages and disadvantages with respect to safety and immunogenicity in different age groups. Potential strategies for the use of these vaccines are presented for the different age and high risk groups.