Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide

Chronic meningococcemia is an uncommon manifestation of meningococcal disease. Our objective was to asses whether a bacterial factor, a mutation in the lpxL1 gene resulting in underacylated lipopolysaccharide, might be important in chronic meningococcemia. We identified 15 patients with chronic meningococcemia over a 50-year period. Chronic meningococcemia episodes were defined by a febrile episode of at least one week and presence of meningococci in blood and/or cerebrospinal fluid (CSF). Meningococcal isolates from these patients were characterised by serogrouping, multi-locus sequence typing, and in vitro interleukin 6 inducing capacity. lpxL1 gene mutations were determined by direct sequencing. The median age was 21 years (range, 2-62) and median duration of symptoms before diagnosis was four weeks (range, 1-12). Of the 15 isolates, seven (47%) strains had a reduced interleukin 6 inducing capacity and were found to have a mutation in lpxL1 resulting in penta-acylated lipid A. This frequency is higher than previously reported among adult patients with meningococcal meningitis (7%; p < 0.0001) and invasive meningococcal disease (9%; p = 0.001). We conclude that chronic meningococcemia patients are often infected with meningococci with a mutation in lpxL1 resulting in underacylated lipid A. The lpxL1 mutations may well explain the protracted and benign clinical course in these patients