Study plans

Pnc-Euro is divided into six workpackages (WPs). Five of the WPs address specific but closely related scientific questions regarding Pnc infection. The sixth WP acts as a conduit for the five other WPs and for the exploitation and dissemination of results.

Factors affecting the reported rates of invasive Pnc disease (WP1)

A description of the availability of surveillance data on invasive Pnc disease will be undertaken. The study will draw together information about surveillance of Pnc invasive disease, careseeking and referral practises for potential disease cases, and differences in admission rates for syndromes that can represent invasive Pnc disease. The sensitivity of the surveillance systems to detect microbiologically diagnosed Pnc disease will be investigated using national or sentinel area approaches.

The development of serological methods to measure and interpret markers of Pnc protection in the population (WP2)

Improved serological techniques to measure natural immunity to S. pneumoniae will be developed . The methods to obtain this include shifting the focus from polysaccharide antibodies to non-serotype specific antibodies and increasing the sensitivity of opsonophagocytic assays. To validate the techniques and to identify correlates for protection, the new methods will be applied to sera currently available from the participants.

Upper respiratory carriage and transmission of Pnc (WP3)

Study protocol (pdf 203kb, for study group only, password access)

Transmission of Pnc carriage will be analysed from longitudinal data sets gathered from groups of individuals with close contacts (families and day care groups). Statistical analyses will be based on epidemic models and Markov chain Monte Carlo (MCMC) sampling methods. The prevalence and incidence of Pnc carriage in different age groups as well as the importance of families and day care groups as sources of Pnc transmission in the population will be estimated. Results will be contrasted to those from recent Pnc conjugate vaccine trials (e.g. Finnish Otitis Media Study) in relation to upper respiratory tract Pnc replacement and other vaccination-related changes.

Modelling the short and long-term effects of different vaccination strategies on Pnc carriage and invasive disease in different populations (WP4)

In connection with WP1, a model of the surveillance system for invasive Pnc disease will be constructed, which formalises the concept of case under-ascertainment by the surveillance system due to a variety of factors. A stochastic model will be used to quantify the effects of these factors on the observed Pnc rates and estimate the actual rates of disease in the participating areas. Based on results from WP3, epidemiological data will be incorporated into mathematical transmission models of Pnc carriage in different populations. Stochastic simulation and deterministic modelling techniques will be used to explore questions related to vaccine policy such as the effect of vaccination coverage and age at vaccination on the distribution of Pnc carriage and disease.

The economic impact of different vaccination strategies on invasive Pnc disease (WP5)

Results from WP1 will be used to calculate the financial burden of invasive Pnc disease, when combined with costs associated with physician consultations and the number of inpatient days. Indirect costs to the community and the individual will be assessed as well. To calculate the economic impact of a large-scale vaccination campaign, estimates of the future costs associated with the vaccine/vaccination will be accompanied by estimates on the effectiveness of vaccination, including any indirect effects. Results of modelling the spread of Pnc in the population (WP4) will be used to address this question.