Further details
The Problem
Meningococcal disease remains a major childhood infection in Europe, with an appreciable number of cases in other age groups, notably young adults. There is currently no comprehensive childhood vaccine against this disease, the severity of which, combined with its rapid progression and non-specific symptoms, results in an unacceptable burden of childhood morbidity and mortality. In addition, the emergence of meningococci with reduced penicillin susceptibility is a major concern. The public health management policies and the development of effective vaccines are confounded by the epidemiology of meningococal disease, which is itself governed by the complex population biology of the causative organism.
Aim
An improved understanding of the spread of hyperinvasive and antibiotic resistant meningococci throughout Europe will be obtained by integrated epidemiological and population genetic studies that employ the latest molecular isolate characterisation techniques (MLST) and electronic data transfer via the Internet. Strain collections from all parts of Europe, in combination with surveillance data, will be analysed for the rigorous definition of hyperinvasive strains. This will help to determine the distribution of meningococcal lineages associated with disease.
The hypothesis that the spread of antibiotic resistant strains is linked to antibiotic usage, and therefore different in different parts of Europe, will be investigated. Collections of isolates with representative levels of antibiotic resistance throughout Europe will be made and isolates characterised by both MLST and nucleotide sequence analysis of the genes encoding antibiotic resistance. Elucidation of the underlying resistance mechanisms and the dynamics of distribution of resistance genes among clonal lineages will be investigated with the intention of tracking and ultimately predicting the spread of antibiotic resistance in these organisms.
There is evidence that particular hyperinvasive lineages are also hypervirulent, that is are likely to cause severe meningococcal disease and death. This will be examined by characterising by MLST the isolates obtained from large numbers of patients with known severity of meningoicoccal disease as assessed by a variety of clinical scoring paradigms. These data will permit the establisment of rigorous definitions of hypervirulent meningococci and will also promote the unification of clinical scores, with the potential to improve clinical management throughout.
Expected results
An enhanced infrastructure for studies and surveillance of meningococcal disease will be created and molecular methods disseminated throughout the Community. Rigorous definitions of disease-associated and antibiotic resistant meningococci, and an understanding of meningococcal population biology and the spread of meningococcal disease, will be generated. The project will provide the infrastructure and the insights essential for harmonised and improved public health and clinical management.
Potential applications
An important and novel element of exploitation and dissemination of the results of this project will be the creation of websites, which will allow (i.) the real time data deposition into databases; (ii.) the distribution of regular summaries of the epidemiological and strain characterisation data; and (iii.) the dissemination of regular updates of the guidelines for the public health and clincal management of meningococcal disease. This information will be of great utility to those public health institutions with responsibility for management of cases and outbreaks of meningococcal disease.
Since all of the national meningococcal reference laboratories in Europe are participants in the consortium, by virtue of their membership of the European Monitoring Group on Meningococci (EMGM), information on latest technologies and newest methods available for the detection and typing of meningococci will automatically be made available Europe-wide. This guarantees that, within a short period of time, unified methods will be applied in all reference laboratories of the Community and that expertise and experience will be shared widely.