||RSV is considered the major viral respiratory tract pathogen of early childhood, and RSV is the most common single cause of childhood hospitalisation in high-income countries. Recent data suggest that RSV hospitalisation rates may be increasing. No vaccine or causal therapy against RSV is available, and the price of prophylactic antibody treatment (palivizumab) restricts its use to infants and children with medical risk factors in high-income countries and prohibits use in low-income countries. Groups at risk of severe disease include preterm infants, infants with pulmonary disease such as chronic lung disease, infants with congenital heart disease, and infants suffering from immunodeficiency. However, most infants getting severely ill from RSV are otherwise healthy and born at term, and among healthy infants factors related to transmission and intensity of exposure are likely determinants of severe infection.
The immunological factors responsible for protection against RSV infection are not completely defined. RSV vaccine trials observed more severe RSV illness among RSV-vaccine recipients, this possibly being related to a Th2 imbalance in the immune response following an inactivated vaccine. Animal studies have found Th2 cytokine responses in those with more severe clinical and pathological disease, and studies in humans have established an association between severe RSV infection and atopy, an immune disorder of exuberant Th2 activity. Hence, the symptomatology of RSV infection seems associated with the immunological state of the host. The present PhD thesis aimed to study determinants of severe RSV infection with a focus on transmission factors and host immunity.
- That increased severity of RSV infection following cross-sex transmission from mother to son in infancy might partly explain why boys have more severe RSV infection. The cross-sex phenomenon was most pronounced in the rainy season
- That BCG vaccination and BCG scar were associated with a decreased risk of ALRI and RSV-ALRI, the associations being most marked in girls and during the rainy season
- That future studies of RSV epidemiology in Danish infants can be based on data from the DNP
- That asthmatic disposition, wheezing and asthma increased the risk of subsequent RSV hospitalisation, suggesting that infants and children who get severe RSV infection might have hypersensitive airways already
- That RSV-MNabs reduced the risk of RSV hospitalisation in early infancy, also among infants with asthma, the association being most pronounced in girls
- That RSV-MNabs increased the risk of asthma and asthma after RSV hospitalisation in early infancy, the association being most pronounced in boys
In conclusion, the studies of the present thesis suggest that the immunologic state of the host is a strong determinant of the severity of RSV infection. Furthermore, our results point towards significant immune differences between the sexes. The results may have implications for vaccine development and policies. Basic immunologic studies of the interaction between host immunology and RSV infection are warranted. Specifically, studies are needed of the interactions between RSV antibodies, RSV infection and the development of asthma, and of the immunologic differences between the sexes.