AbstractYoung Indigenous children living in remote central and northern Australia suffer a heavy burden of rotavirus and other diarrhoeal diseases. In October 2006, the human rotavirus vaccine (Rotarix™, GSK) was introduced into the routine vaccination schedule for all Northern Territory (NT) infants. The studies in this thesis aim to evaluate the impact of rotavirus vaccination in the NT on serious (hospitalised) disease in children.
Active hospital-based surveillance was undertaken for two years at both major hospitals in the NT in order to ascertain hospitalisations for gastroenteritis and to assemble a control-cohort of children admitted with respiratory symptoms. Children were tested for rotavirus by enzyme immunoassay (EIA), and tested for other enteric pathogens using a combination of microscopy, culture and molecular methods. A case-cohort analysis was used to determine the effectiveness of rotavirus vaccination against hospitalisation for gastroenteritis. The results were validated using a conventional hospital-based case-control analysis, and also a cohort analysis nested within the Northern Territory Immunisation Register (NTIR).
Over the study period, 479 hospitalisations for gastroenteritis were ascertained, of which 132 were rotavirus-confirmed. This included 71 (54%) mixed infections which were also positive for a non-rotavirus pathogen. By the primary analysis, vaccine effectiveness (VE) was 59% (95%CI: 30 to 76%) against hospitalisations for rotavirus-confirmed gastroenteritis and 29.4% (95%CI: -4.3 to 52.3) against all-cause gastroenteritis. VE point estimates were lower among older children and against mixed infections. Estimates based on the case-control and register cohort analyses were similar.
Rotavirus vaccination prevents hospitalisation in this setting, especially among young infants who are most susceptible to severe disease. However VE is lower than reported elsewhere in the developed world. The finding of reduced effectiveness among older children infected with heterotypic rotavirus strains and among children co-infected with non-rotavirus enteric pathogens, may provide an insight into the mechanisms underlying vaccine failure in high burden settings. Further reduction of the total burden of diarrhoeal disease in the NT is likely to require both improved vaccination strategies as well as basic improvements in hygiene, sanitation, and housing.
|Date of Award||Dec 2011|
|Supervisor||Jonathan Carapetis (Supervisor) & Ross Andrews (Supervisor)|