Neipseria meningitedis in Brazil: implantation of new method for molecular diagnosis and genetic characterization for Multilocus Sequence Typing - MLST
In the last 10 years, meningococcal disease in Brazil, has presented endemic features and high lethality rates. In some states like Rio de Janeiro, recent data show a 100% increase in the lethality rate, with no changes in the number of cases. These high lethality rates and the occurrence of outbreaks throughout the country have led us to analyze isolates from different Brazilian regions, by the method of Multilocus Sequence Typing (MLST). This method has been considered the ?gold standard? for the determination of epidemic and hypervirulent clones in Neisseria meningitidis populations. After the sequencing of seven housekeeping genes coding for constitutive enzymes and submission of the sequences to the MLST database, new Sequence Types (STs) have been determined or associated to an existing ST. Our goal was to analyze 84 strains isolated in 4 Brazilian states in the period ranging from 1999 to 2003 in order to assess not only the genetic evolution of this microorganism in Brazil and the presence of new epidemic and hypervirulent related clones, but also the possible changes in the genetic diversity and epidemiologic patterns after the vaccination campaigns carried out in the past using A/C vaccines and a B/C vaccine which showed low efficacy. The results obtained by Multilocus Enzyme Electrophoresis (MEE) and MLST show the presence of 4 hypervirulent clonal complexes and a number of new clones, most of them related to hypervirulent clones. The prevalence of ST-639, which is found only in Brazil and is genetically related to the hypervirulent complex ST-32/ET-5, and of strains related to the clonal complex ST-11/ET-37, is a concerning issue, since these clonal complexes have already caused outbreaks in other countries, showing high lethality rates. The association of these clonal complexes to serogroup B, C and W135 strains and the increasing rates of isolation of these serogroups during the last years is another important issue, alerting to the need of improving the control of meningococcal disease in Brazil. The development of a more sensitive and specific molecular method for the diagnosis of meningococcal disease, directly from clinical samples after negative results by conventional laboratory methods, has been described and proposed as a new tool for the rapid diagnosis of this life threatening disease, which can kill in a few hours after the onset of symptoms.
Advisor:Ana Carolina Paulo Vicente; Hooman Momen
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Neipseria meningitedis Multilocus Sequence Typing (MLST) Diagnóstico Molecular Neisseria meningitidis Diagnosis Enzyme Electrophoresis (MEE) BACTEROLOGIA
Date of Publication:05/31/2005