Sibling familial risk ratio of meningococcal disease in UK Caucasians

To quantify the host genetic component of meningococcal disease (MD) susceptibility, the sibling risk ratio (λs) was calculated as the ratio of observed MD cases among 845 siblings of 443 UK Caucasian cases to that expected, calculated from age-calendar year specific rates for England and Wales. Twenty-seven siblings contracted MD compared with an expected 0·89, generating a λs value of 30·3. Overestimation of λs due to Neisseria meningitidis exposure was minimized by excluding siblings with MD onset within set time points of the index case. Irrespective of whether siblings contracted MD more than 1, 3, 6, 9 or 12 months after the index case, the λs varied slightly (λs range: 8·2–11·9), suggesting that host genetic factors may contribute approximately one third of the total λs. Social class distribution did not differ between MD cases and the general population of England and Wales. This study is the first to calculate λs for MD and establishes that susceptibility to MD has a significant host genetic component.

[1]  J. Nguyen-Van-Tam,et al.  Seven-week interval between acquisition of a meningococcus and the onset of invasive disease. A case report , 1999, Epidemiology and Infection.

[2]  Morgan,et al.  Properdin deficiency and meningococcal disease—identifying those most at risk , 1999, Clinical and experimental immunology.

[3]  Schaad,et al.  Properdin deficiency in a large Swiss family: identification of a stop codon in the properdin gene, and association of meningococcal disease with lack of the IgG2 allotype marker G2m(n) , 1999, Clinical and experimental immunology.

[4]  H. Tobi,et al.  Upper respiratory tract infection, heterologous immunisation and meningococcal disease. , 1999, Journal of medical microbiology.

[5]  A. Gilmore,et al.  Meningococcal disease at the University of Southampton: outbreak investigation , 1999, Epidemiology and Infection.

[6]  M. Hibberd,et al.  Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease , 1999, The Lancet.

[7]  D. Stephens Uncloaking the meningococcus: dynamics of carriage and disease , 1999, The Lancet.

[8]  L. Berthelsen,et al.  Dynamics of the meningococcal carrier state and characteristics of the carrier strains: a longitudinal study within three cohorts of military recruits , 1998, Epidemiology and Infection.

[9]  M. K. Ghosh,et al.  Epidemiology of meningococcal carrier state amongst recruits of a military training centre. , 1995, The Journal of communicable diseases.

[10]  F. Sisay-Joof,et al.  Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children. , 1995, The Journal of infectious diseases.

[11]  D. Graham,et al.  Helicobacter pylori Infection: Genetic and Environmental Influences: A Study of Twins , 1994, Annals of Internal Medicine.

[12]  P. Andersen,et al.  Genetic and environmental influences on premature death in adult adoptees. , 1988, The New England journal of medicine.

[13]  K. Cartwright,et al.  The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica , 1987, Epidemiology and Infection.

[14]  P. Densen,et al.  Complement Deficiency States and Infection: Epidemiology, Pathogenesis and Consequences of Neisserial and Other Infections in an Immune Deficiency , 1984, Medicine.

[15]  P. Fine Immunogenetics of susceptibility to leprosy, tuberculosis, and leishmaniasis. An epidemiological perspective. , 1981, International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association.

[16]  Comstock Gw Tuberculosis in twins: a re-analysis of the Prophit survey. , 1978, The American review of respiratory disease.

[17]  I. Goldschneider,et al.  Carriage of Neisseria meningitidis and Neisseria lactamica in infants and children. , 1978, The Journal of infectious diseases.

[18]  E. Edwards,et al.  Evaluation of group C meningococcal polysaccharide vaccine in marine recruits, San Diego, California. , 1970, American journal of epidemiology.

[19]  J. Mueller,et al.  MENINGOCOCCUS CARRIER RATES AND MENINGITIS INCIDENCE , 1950, Bacteriological reviews.

[20]  Aycock Wl,et al.  MENINGOCOCCUS CARRIER RATES AND MENINGITIS INCIDENCE , 1950 .

[21]  A. Hill,et al.  The genomics and genetics of human infectious disease susceptibility. , 2001, Annual review of genomics and human genetics.

[22]  D. Kwiatkowski Genetic dissection of the molecular pathogenesis of severe infection , 2000, Intensive Care Medicine.

[23]  G. Comstock Tuberculosis in twins: a re-analysis of the Prophit survey. , 1978, The American review of respiratory disease.

[24]  H. Ward,et al.  Immunological investigations of meningococcal disease. III. Brevity of group C acquisition prior to disease occurrence. , 1977, Scandinavian journal of infectious diseases.

[25]  P. Sheehe,et al.  Meningococcal carriage in a population of "normal" families. , 1971, The Journal of infectious diseases.