Genetics in Meningococcal Disease: One Step Beyond

Abstract

emerged in the 1990s, creating useful tools for meningococcal disease. The standard for epidemiologic research has become multilocus sequence typing. Multilocus sequence typing analysis determines genetic variation in 7 housekeeping genes of the meningococcus and has shown that most cases of disease are caused by a few clonal complexes of related sequence types, the hypervirulent lineages [8, 9]. As a diagnostics tool, PCR has shown to be a highly sensitive test in meningococcal disease [10]. Meningococcal DNA detection by PCR has been used in Great Britain since 1996 and can be regarded as a routine diagnostic test in patients with suspected meningococcal disease. Quantitative PCR to determine bacterial load has not been broadly implemented, and its clinical value still has yet to be assessed. New genetic research techniques have also identified host genetic polymorphisms that influence severity and outcome in meningococcal disease. A clear association between mortality and meningococcal disease was found for polymorphisms in the IL-1 (IL-1), IL-1 receptor antagonist (IL-1RN), and plasminogen activator inhibitor 1 (SERPINE1) genes (figure 1) [5–7, 11–13]. For these genes, 8 different polymorphisms have been described in 6 studies, which included a total of 2534 patients. The median mortality rate among patients included in these studies was 7% (range, 1%–19%). Diagnosis was microbiologically confirmed in 4 of 6 studies; 2 studies also included patients with a clinical picture of meningococcal disease without microbiological confirmation. We performed a meta-analysis of available studies and reported that the polymorphisms PAI 4G/5G, IL1-RA +2018C/T, and IL-1B -511C/T were related to death, with ORs of 2.3 (95% CI, 1.5–3.5), 1.9 (95% CI, 1.3–2.9), and 1.8 (95% CI, 1.1–3.1), respectively.