TY - JOUR
T1 - Prevalence and Clinical Course in Invasive Infections with Meningococcal Endotoxin Variants
AU - Rodenburg, Gerwin D.
AU - Fransen, Floris
AU - Bogaert, Debby
AU - Schipper, Kim
AU - Groenwold, Rolf H. H.
AU - Hamstra, Hendrik Jan
AU - Westerhuis, Brenda M.
AU - van de Beek, Diederik
AU - van der Ley, Peter
AU - Sanders, Elisabeth A. M.
AU - van der Ende, Arie
PY - 2012
Y1 - 2012
N2 - Background: Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their IpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation. Methods: A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The IpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records. Results: Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95% CI 0.09-0.58) and were less often admitted to intensive care (OR 0.21; 95% CI 0.07-0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics. Conclusions: In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course
AB - Background: Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their IpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation. Methods: A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The IpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records. Results: Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95% CI 0.09-0.58) and were less often admitted to intensive care (OR 0.21; 95% CI 0.07-0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics. Conclusions: In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course
U2 - https://doi.org/10.1371/journal.pone.0049295
DO - https://doi.org/10.1371/journal.pone.0049295
M3 - Article
C2 - 23209568
SN - 1932-6203
VL - 7
SP - e49295
JO - PLOS ONE
JF - PLOS ONE
IS - 11
ER -