Objetivo Monitoring of capsular polysaccharides (serogrouping) and outer membrane proteins (serotyping and subtyping) of pathogenic meningococci is the basic method of epidemic surveillance. Additionally, information is obtained for the development and application of meningococcal vaccines. Results from a previous INTAS-granted collaborative study of the Dutch Reference Laboratory and the Moscow Reference Laboratory in 1995-96, showed that the 80% of all meningococcal isolates in Russia were phenotypically untypeable. Since cultures from only 30% of clinical cases of meningococcal meningitis yielded a Neisseria meningitidis, the precise distribution of the various N. meningitidis types and subtypes in Russia is unknown.The development and application of molecular biological techniques enable to diagnose bacterial meningitis and to fingerprint the causative strain irrespctive of the results of conventional culture methods. The first major objective of this combined research proposal is to obtain complete phenotypic and genetic information of the bacteria causing meningitis in Moscow, with the goal of using this information for the development of vaccination programs and clarification of evolutionary relationship of strain. The new developed typing methods in Amsterdam and the automated DNA sequencing approach at the Institute for Molecular Genetics (Germany) will be used. The second topic is to study the host defence mechanisms against meningococcal disease with special emphasis to the complement-dependent lysis and phagocytic killing of meningococci isolated from various clinical manifestations of meningococcal disease (meningitis, fulminant septic shock or chronic meningococcemia).The complement deposition on the meningococcal surface and its influence by acute phase proteins and regulatory complement components will be investigated in detail using well characterised meningococcal strains. If quantitavely important modes of complement activation are found, these will be studied comparing patients' strains and collected serum samples. These in vitro findings will be compared with clinical features of meningococcal disease, including case-fatality, complications and sequela. Both genetic characteristics and complement resistance of strains will be correlated with the severity and outcome of disease. The results of this project will enable European and Russian Laboratories to overcome the diagnostic problems caused by early antibiotic treatment. The genetic typing methods will be standardised internationally and used to replace the currently used cumbersome and partial phenotypic assays. The immunological studies will identify the groups of individuals having an increased risk to contract meningococcal disease and clarify the problem of host-pathogen interactions in such individuals. Finally, the results will lead to recommendations for vaccination programs. Programa(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Tema(s) 4 - Life Sciences INTAS - INTAS Convocatoria de propuestas Data not available Régimen de financiación Data not available Coordinador Leids University Medical Center Aportación de la UE Sin datos Dirección P.O. Box 9600 2300 RC Leiden Países Bajos Ver en el mapa Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Central Research Institute of Epidemiology Rusia Aportación de la UE Sin datos Dirección Novogireevskaya uliza 3A 111123 Moscow Ver en el mapa Coste total Sin datos Leopold-Franzens University Austria Aportación de la UE Sin datos Dirección Fritz-Pregl-Strasse 3 6020 Innsbruck Ver en el mapa Coste total Sin datos Max-Planck-Gesellschaft Alemania Aportación de la UE Sin datos Dirección Ihnestrasse 73 14195 Berlin Ver en el mapa Coste total Sin datos Moscow Medical Institute Rusia Aportación de la UE Sin datos Dirección Bolshaya Gruzinskaya, 56 123056 Moscow Ver en el mapa Coste total Sin datos
