Molecular typing methods for Neisseria meningitidis

Neisseria meningitidis is an important pathogen because it causes life-thre atening infections, The rapid course of meningococcal disease and the capac ity of some serogroups to cause large-scale epidemics necessitates the use of sensitive, reliable and rapid typing methods to characterise strains. Mo lecular typing techniques for N. meningitidis are used for epidemiological purposes to investigate outbreaks and the spread of organisms and to examin e the population genetic structure of the organism to understand better its variation and evolution. Many investigators have employed molecular typing methods and shown that meningococcal disease is associated,vith a variety of different epidemiological patterns. The choice of a typing method is dep endent upon the epidemiological questions to be answered and on the populat ion genetics of the organism under investigation. With highly clonal popula tions comprising independent non-recombining lineages such as serogroup A m eningococci, ribotyping, multilocus enzyme electrophoresis (MLEE), pulsed-f ield gel electrophoresis (PFGE), multilocus sequence typing (MLST), PCR wit h arbitrary primers (RAPD) or with other gene-based primers each provides a constant measure of the relationship between strains. A more restricted po rtfolio of molecular methods - PFGE, MLEE and MLST - is appropriate for the investigation of less clonal serogroup B and C meningococci from localised outbreaks, If a thorough evaluation of the overall population is sought to determine the relationship between new isolates and members of hyper-endem ic clonal complexes then quantitative methods such as MLEE and MLST are nec essary. Several PCR-based methods are used for the detection and typing of meningococcal strains, many requiring rigorous standardisation before they can be considered suitable for rapid and reliable differentiation between c lones. This review examines strain characterisation by molecular techniques and non-culture-based subtyping of meningococci in clinical specimens, It assesses the importance of these techniques and examines the epidemiologica l questions that they answer and also their limitations.