Neisseria meningitidis phenotypic markers and septicaemia, disease progress and case-fatality rate of meningococcal disease: a 20-year population-based historical follow-up study in a Danish county

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Abstract
The incidence rate (IR) and case-fatality rate (CFR) of meningococcal disease increased during the late 1980s and early 1990s in North Jutland County, Denmark. We examined the hypothesis that phenotypic markers of Neisseria meningitidis are predictors of septicaemia with or without meningitis, rapid disease progress and fatal outcome of meningococcal disease and we studied whether changes in IR and CFR over time might be related to emergence or spread of certain phenotypes. This follow-up study was based on a complete registration of 413 cases of meningococcal disease in North Jutland County during 1980–99. Phenotypic markers included serogroup, serotype and serosubtype. A complete phenotype was available for 315 cases (76 %); 100 (32 %) strains were phenotype B : 15 : P1.7,16 and 31 (10 %) were C : 2a : P1.2,5. Septicaemia without meningitis was less common in cases with B : 15 : P1.7,16 and C : 2a : P1.2,5 strains. No association was found between phenotype and rapid disease progress. The overall CFR was 12 %. An increased CFR was associated with phenotypes B : 15 : P1.7,16 [odds ratio (OR) 2.8, 95 % confidence interval (CI) 1.2–18.5] and C : 2a : P1.2,5 (OR 5.2, 95 % CI 1.6–16.4) when compared with other phenotypes. The prevalence of B : 15 : P1.7,16 strains increased gradually during the study period and the CFR increased from 8 % during 1980–89 to 19 % during 1990–99, although the CFR for other phenotypes also increased. The CFR for C : 2a : P1.2,5 remained high (∼20 %), but the contribution of this phenotype to the overall CFR decreased during the study period. In conclusion, phenotypes B : 15 : P1.7,16 and C : 2a : P1.2,5 were predictors of an increased CFR. The high prevalence of phenotype B : 15 : P1.7,16 contributed to increased overall IR and CFR during 1990–99.