Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens, such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole-genome amplification (SWGA), an isothermal multiple-displacement amplification-based method, to efficiently enrich, sequence, and de novo assemble N. meningitidis DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of N. meningitidis reads by 2 to 3 orders of magnitude, enabling identification of at least 90% of the 1,605 N. meningitidis core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial loads were processed by SWGA before sequencing, and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the N. meningitidis pathogen, thus enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rates. SWGA produces enough reads for phylogenetic and allelic analysis at a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.
 ...
PMID:Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation. 3293 38

Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) are pathogenic bacteria that can cause human infections. While Nm infections are associated with bacterial meningitis and bacteremia, a strain of Nm, isolated from the urogenital system, has recently been associated with urethritis. As this strain is becoming prominent as an emerging pathogen, it is essential to assess identification tools for Nm and Ng urogenital isolates. Consecutive Nm isolates recovered from urogenital cultures of symptomatic patients with presumptive diagnoses of gonorrhea and a random selection of Ng isolates recovered from the same population within the same time frame were characterized with routine identification systems, antimicrobial susceptibility testing, and whole genome sequencing. MALDI-ToF MS, multilocus sequence typing, 16S rRNA gene sequence, and average nucleotide identity methods accurately identified 95% (18/19) of Nm and Ng isolates. 30% (3/10) of Nm isolates were misidentified as Ng with Aptima Combo 2 CT/NG but no misidentifications were found with the Xpert CT/NG NAAT. Phylogenetic core genome and SNP-based grouping analyses showed that urogenital Nm isolates were highly related, and phylogenetically distinct from Ng and respiratory Nm isolates but similar to urogenital Nm isolates from patients with urethritis in the US. Urogenital Nm isolates were predominantly azithromycin resistant while Ng isolates were azithromycin susceptible. These data indicate that urogenital isolates of Nm can cause false-positive detections with Ng diagnostic assays. Misidentification of urogenital Nm isolates may confound public health-related activities for gonorrhea and future studies are needed to understand the impact on clinical outcome of Nm urogenital infection.
 ...
PMID:Genomic characterization of emerging bacterial uropathogen Neisseria meningitidis misidentified as Neisseria gonorrhoeae by nucleic acid amplification testing. 3317 23