Sibling familial risk ratio of meningococcal disease in UK Caucasians

Haralambous, Elene; Weiss, Helen A.; Radalowicz, A; Hibberd, Martin L.; Booy, Robert; Levin, Michael

doi:10.1017/s0950268803008513

Cited by 54 publications

(34 citation statements)

References 21 publications

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“…Furthermore, many different host genetic and immunological factors are associated with meningococcal disease 1–3 5 10 11. These can be associated with a much longer timescale between familial cases, often across extended families and even generations.…”

Section: Discussionmentioning

confidence: 99%

A cluster of four cases of meningococcal disease in a single nuclear family

Acheson¹,

Barron

Borrow³

et al. 2012

Arch Dis Child

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A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family across a 15-week period. The cases were three siblings and a parent and all recovered well. The first case was confirmed by meningococcal PCR only but the subsequent three cases were due to indistinguishable strains of serogroup B (B:NT:P1.19-1,15-11). Contact tracing was initially undertaken and reviewed in detail after each subsequent case. Antibiotic prophylaxis was administered to close family contacts on three separate occasions, including switching of antibiotic agents, with good compliance. Subsequent investigation of the family has not revealed any obvious immunological problem and no further significant infections have been recognised. A cluster of meningococcal disease of this nature and timescale is highly unusual. Details of the cluster, investigation and implications for health protection practice are discussed.

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Section: Discussionmentioning

confidence: 99%

A cluster of four cases of meningococcal disease in a single nuclear family

Acheson¹,

Barron

Borrow³

et al. 2012

Arch Dis Child

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“…Individual susceptibility to exposure and outcome shows a great interindividual variability, suggesting that genetic factors may play an important role (Haralambous et al 2003;Sorensen et al 1988). Many gene polymorphisms have already been associated with susceptibility or outcome of severe sepsis (Texereau et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia

et al. 2007

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Meningococcal disease may present as sepsis, meningitis or a combination of both. Protein C (PC) is an important regulator of thrombin activity. Two polymorphisms in the promoter region of PC (C-1654T, A-1641G) have been shown to affect PC levels. In patients with meningococcal sepsis, low PC levels have been correlated with increased severity and poor outcome. We established a multicenter case-control study to determine whether PC promoter polymorphisms are associated with occurrence and outcome of meningococcal disease and sepsis. 288 previously healthy children with meningococcal infection from 97 pediatric hospitals in Germany, Switzerland, Italy, and Austria and 309 healthy controls were included in the study. A strong age-dependant effect was found. Patients younger than 1 year carried significantly more often the CG-CG genotype than healthy controls (28.6% vs. 17.8%, P = 0.04). Carriers of the CG allele showed a 3.43-fold increased odds ratio (OR) to develop sepsis (95% CI: 1.05-11.20; 85.7% vs. 63.6%, P = 0.036). The TA-TA genotype conferred a protective role for the development of sepsis (P = 0.017) with a Haldane OR of 0.09 (95% CI: 0.01-0.94). Systolic blood pressure values were significantly decreased in patients carrying the CG-CG genotype (70 vs. 86 mmHg, P = 0.005), and the need for adrenergic support significantly higher (70% vs. 26%, P = 0.018), resulting in an OR of 6.61 (95% CI: 1.28-34.14). These findings show that in young children PC promoter genotype is associated with susceptibility for meningococcal disease, the development of meningococcal sepsis, lower blood pressure, and need for adrenergic support.

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“…Diagnosis of MD was made in patients presenting with a characteristic purpuric or petechial rash, and clinical evidence of meningitis and/or septicaemia61819. Diagnosis was confirmed microbiologically by culture of N. meningitidis from blood or CSF, or by PCR for meningococcal DNA in blood.…”

Section: Methodsmentioning

confidence: 99%

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

Martinón‐Torres¹,

Png²,

Khor³

et al. 2016

Sci Rep

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Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

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Sibling familial risk ratio of meningococcal disease in UK Caucasians

Cited by 54 publications

References 21 publications

A cluster of four cases of meningococcal disease in a single nuclear family

A cluster of four cases of meningococcal disease in a single nuclear family

Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

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