Population-based Studies of Invasive Pneumococcal Disease in Denmark. Childhood Risk Factors and Familial Aggregation
PhD thesis, University of Copenhagen, 2007
By Thomas Hjuler
Department of Epidemiology Research
Statens Serum Institut
Invasive pneumococcal disease (IPD) is a serious health problem worldwide causing substantial morbidity and mortality. In many countries, including Denmark, Streptococcus (S.) pneumoniae is the most common cause of meningitis and a leading cause of bacteremia. For these reasons, studies of risk factors and the basic epidemiology of IPD are of importance for clinicians as well as for the vaccine community.
The Pneumococcus Database was established based on nationwide laboratory surveillance of IPD in patients hospitalized in Denmark since 1938. Denmark’s systems of registry-based data offered a unique opportunity to examine risk factors and familial aggregation of IPD through linkage of the Pneumococcus Database with other national data sources.
To examine perinatal and crowding-related risk factors for IPD in infants and young children, we set up a matched case-control study nested in the Danish population. Analyses showed that infants born preterm or with low birth weight were at increased risk of IPD. Having older siblings increased the risk of IPD in infants aged less than 6 months. In contrast, children aged 6-23 months who had older siblings were at reduced risk of IPD, indicating that they had obtained natural immunization from infection. The same effect of crowding was observed in relation to day care attendance. Thus, children were at increased risk of IPD the first months after day care enrollment, but subsequently at a reduced risk, likely because of naturally acquired immunity from infection. Our results add further knowledge to how exposure to other children is associated with IPD, but immunity appeared to occur rapidly from natural exposure.
Another population-based case-control study was set up to quantify IPD risk in a wide range of chronic diseases among children. Children with cancer or chronic renal disease and those undergoing splenectomy or transplantation were particularly susceptible, perhaps because each of these conditions is associated with immune suppression. IPD risk increased with the number of hospital contacts for any reason. Adjusted for the number of hospital contacts, risk in children with other chronic diseases was 1.4-fold higher than in those with a hospital contact for any other reason. The results indicate that children with other chronic diseases are likely to be more susceptible to IPD only because they have more hospital contacts. The most likely explanation is that there is a progressive increase in the proportion of frail children with repeated hospital contacts
Genetics may influence susceptibility to infectious diseases. To test this hypothesis we examined familial aggregations of invasive infections, using IPD as the index condition to identify families at risk in a nationwide cohort. No aggregation of invasive infections among IPD relatives was observed, other than for events within the first year among relatives who most likely shared the same household. Thus, at the population level, environmental rather than genetic factors are the important contributors for development of IPD and other major infections.
Using nationwide registry information on Respiratory Syncytial Virus (RSV) hospitalization linked with the Pneumococcus Database, we examined the association between RSV hospitalization and IPD and vice versa in a prospective population-based cohort study. In our cohort, an increased risk of IPD was observed the following 30 days after an RSV- or non-RSV respiratory hospitalization in children below two years of age. IPD did not increase the risk of RSV hospitalization in children aged below two years.
Infection with S. pneumoniae is almost universal and occurs at an early age, IPD being a rare, but serious clinical outcome. Naturally acquired immunization from infection occurs rapidly after exposure, but the primary infection may cause IPD. Young children with coincident upper respiratory tract infection and children with repeated hospitalizations due to severe disease are particularly susceptible. At the population level, environmental rather than genetic factors are the important contributors for development of IPD. Even though high-risk groups can be identified, the majority of IPD cases occur in previously healthy children, underscoring the importance of early national pneumococcal vaccination.
Sidst redigeret 29. juni 2010