What is the prevalence of primary immunodeficiency in children and young people with meningococcal disease?

Bibliographic informationReason for exclusion
N. A. Bishof, T. R. Welch, and L. S. Beischel. C4B deficiency: a risk factor for bacteremia with encapsulated organisms. Journal of Infectious Diseases 162 (1):248–250, 1990This study includes only 4 children with Neisseria infection. The sample size is too small for useful interpretation of results.
H. F. Eichenwald. Complement deficiencies in patients over ten years old with meningococcal disease due to uncommon serogroups: Comment. Pediatric Infectious Disease Journal 9 (1):70, 1990This is a commentary.
R. T. Ellison, III, P. F. Kohler, J. G. Curd, F. N. Judson, and L. B. Reller. Prevalence of congenital or acquired complement deficiency in patients with sporadic meningocococcal disease. New England Journal of Medicine 308 (16):913–916, 1983This study includes only 20 patients. The study includes people of all ages and does not report outcomes for children separately. At least 50% of the study population is adult.
J. Faber, T. Schuessler, A. Finn, C. Murdoch, W. Zenz, P. Habermehl, C. U. Meyer, B. U. Zabel, H. Schmitt, F. Zepp, and M. Knuf. Age-dependent association of human mannose-binding lectin mutations with susceptibility to invasive meningococcal disease in childhood. Pediatric Infectious Disease Journal 26 (3):243–246, 2007This study looks at variants of the MBL gene, but does not report protein levels.
R. J. Fass and S. Saslaw. Chronic meningococcemia. Possible pathogenic role of IgM deficiency. Archives of Internal Medicine 130 (6):943–946, 1972This is not an immune deficiency of interest. This is not a relevant population.
C. A. Fijen, E. J. Kuijper, H. G. Tjia, M. R. Daha, and J. Dankert. Complement deficiency predisposes for meningitis due to nongroupable meningococci and Neisseria-related bacteria. Clinical Infectious Diseases 18 (5):780–784, 1994This study includes only 6 children with meningococcal meningitis. The sample size is too small for useful interpretation of results.
C. A. Fijen, E. J. Kuijper, A. J. Hannema, A. G. Sjoholm, and J. P. van Putten. (1989) P. Garred, T. E. Michaelsen, G. Bjune, S. Thiel, and A. Svejgaard. A low serum concentration of mannan-binding protein is not associated with serogroup B or C meningococcal disease. Scandinavian Journal of Immunology 37 (4):468–470, 1993This study is eclipsed by the included study by Fijen et al 1999 {46202}. This study includes children and adults but does not report outcomes for children separately.
B. Z. Garty, M. Nitzan, and Y. L. Danon. Systemic meningococcal infections in patients with acquired complement deficiency. Pediatric Allergy and Immunology 4 (1):6–9, 1993This study does not address the clinical question.
B. M. Greenwood, A. M. Greenwood, A. K. Bradley, K. Williams, M. Hassan-King, F. C. Shenton, R. A. Wall, and R. J. Hayes. Factors influencing susceptibility to meningococcal disease during an epidemic in The Gambia, West Africa. Journal of Infection 14 (2):167–184, 1987This is not a relevant population.
E. Haralambous, S. O. Dolly, M. L. Hibberd, D. J. Litt, I. A. Udalova, C. O'dwyer, P. R. Langford, Kroll J. Simon, and M. Levin. Factor H, a regulator of complement activity, is a major determinant of meningococcal disease susceptibility in UK Caucasian patients. Scandinavian Journal of Infectious Diseases 38 (9):764–771, 2006This study investigates the association between a polymorphism in the factor H locus, which leads to increased expression and susceptibility to meningococcal disease. This is not an immune variant included in the question on immune deficiencies.
M. L. Hibberd, M. Sumiya, J. A. Summerfield, R. Booy, and M. Levin. Association of variants of the done for mannose-binding lectin with susceptibility to meningococcal disease. Lancet 353 (9158):1049–1053, 1999This study looks at variants of the MBP gene, but does not report protein levels.
K. Hogasen, T. Michaelsen, O. J. Mellbye, and G. Bjune. Low prevalence of complement deficiencies among patients with meningococcal disease in Norway. Scandinavian Journal of Immunology 37 (4):487–489, 1993This is not a relevant population. The ages range from 15 to 23 years.
R. J. Leggiadro and J. A. Winkelstein. Prevalence of complement deficiencies in children with systemic meningococcal infections. Pediatric Infectious Disease Journal 6 (1):75–76, 1987The study sample size is too small for useful analysis.
S. Maitra and S. K. Ghosh. Recurrent pyogenic meningitis--a retrospective study. Quarterly Journal of Medicine 73 (270):919–929, 1989This is not the population of interest. Most people in the study have intracranial abnormality predisposing to recurrent bacterial meningitis.
J. Merino, V. Rodriguez-Valverde, J. A. Lamelas, J. L. Riestra, and B. Casanueva. Prevalence of deficits of complement components in patients with recurrent meningococcal infections. Journal of Infectious Diseases 148 (2):331, 1983There is insufficient information about the study population and methods of sampling. The study includes people of all ages and does not report outcomes for children separately.
M. Nagata, T. Hara, T. Aoki, Y. Mizuno, H. Akeda, S. Inaba, K. Tsumoto, and K. Ueda. Inherited deficiency of ninth component of complement: an increased risk of meningococcal meningitis. Journal of Pediatrics 114 (2):260–264, 1989This study was conducted in Japan. This is not a relevant population for extrapolation of the prevalence of complement deficiency in UK children with meningococcal disease.
H. E. Nielsen, C. Koch, P. Magnussen, and I. Lind. Complement deficiencies in selected groups of patients with meningococcal disease. Scandinavian Journal of Infectious Diseases 21 (4):389–396, 1989This study does not report the age of the study population or the age of the cases with complement deficiency.
A. Orren, P. C. Potter, R. C. Cooper, and Toit E. du. Deficiency of the sixth component of complement and susceptibility to Neisseria meningitidis infections: studies in 10 families and five isolated cases. Immunology 62 (2):249–253, 1987This is a narrative review.
A. Orren and P. C. Potter. Complement component C6 deficiency and susceptibility to Neisseria meningitidis infections. South African Medical Journal Suid-Afrikaanse Tydskrif Vir Geneeskunde. 94 (5):345–346, 2004This study was conducted in South Africa. This is not a relevant population for extrapolation of the prevalence of complement deficiency in UK children with meningococcal disease.
A. E. Platonov, V. B. Beloborodov, and I. V. Vershinina. Meningococcal disease in patients with late complement component deficiency: studies in the U.S.S.R. Medicine 72 (6):374–392, 1993This study was conducted in the USSR. This is not a relevant population for extrapolation.
A. E. Platonov, G. A. Shipulin, O. J. Shipulina, I. V. Vershinina, and P. Densen. Heterozygous C8beta complement deficiency does not predispose to meningococcal disease. Clinical and Experimental Immunology 108 (3):497–499, 1997This study was conducted in Russia. This is not a relevant population for extrapolation.
A. E. Platonov, G. A. Shipulin, I. V. Vershinina, J. Dankert, J. G. van de Winkel, and E. J. Kuijper. Association of human Fc gamma RIIa (CD32) polymorphism with susceptibility to and severity of meningococcal disease. Clinical Infectious Diseases 27 (4):746–750, 1998This is not a polymorphism of interest.
J. M. Rasmussen, B. Teisner, P. Weihe, B. Mathiassen, T. Petersen, and H. Isager. Screening for complement deficiencies in patients surviving from epidemic meningococcal disease. Journal of Clinical and Laboratory Immunology 25 (4):161–165, 1988This study was conducted in the Faroe islands. This is not a relevant population for extrapolation.
S. Rogde, E. A. Hoiby, P. Teisberg, and B. Olaisen. Genetic aspects of complement component C8 in Norwegian meningococcal disease patients. Scandinavian Journal of Infectious Diseases 22 (6):673–679, 1990This study does not report the age of the study population or the age of the cases with complement deficiency.
P. C. Rowe, R. H. McLean, R. A. Wood, R. J. Leggiadro, and J. A. Winkelstein. Association of homozygous C4B deficiency with bacterial meningitis. Journal of Infectious Diseases 160 (3):448–451, 1989This study includes only 10 children with meningococcal meningitis.
M. Schlesinger, Z. Nave, Y. Levy, P. E. Slater, and Z. Fishelson. Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections. Clinical and Experimental Immunology 81 (3):423–427, 1990This is not a relevant population.
M. Schlesinger, U. Mashal, J. Levy, and Z. Fishelson. Hereditary properdin deficiency in three families of Tunisian Jews. Acta Paediatrica 82 (9):744–747, 1993This study does not address the clinical question.
This is not a relevant population.
D. S. Stephens, R. A. Hajjeh, W. S. Baughman, R. C. Harvey, J. D. Wenger, and M. M. Farley. Sporadic meningococcal disease in adults: results of a 5-year population-based study. Annals of Internal Medicine 123 (12):937–940, 1995This is not a relevant population.
The study involves adults only.
H. Valassi-Adam, T. Thomaidis, B. Syriopoulou, and N. Matsaniotis. Development of meningoccal disease: could it depend on serum IgM levels? Helvetica Paediatrica Acta 30 (4–5):435–440, 1976This is not an immune deficiency of interest.
H. C. Whittle, J. Werblinska, M. Hassan-King, B. M. Greenwood, E. Wolf, H. Festenstein, and Loghem E. van. Is there a genetic immune defect in families with meningococcal meningitis? Journal of Infection 3 (2):140–149, 1981This study does not address the clinical question.
A. Zimran, B. Rudensky, M. R. Kramer, F. Tedesco, M. Ehrenfeld, R. Raz, Z. Greif, M. Gelber, M. Lishner, and E. Golan. Hereditary complement deficiency in survivors of meningococcal disease: high prevalence of C7/C8 deficiency in Sephardic (Moroccan) Jews. Quarterly Journal of Medicine 63 (240):349–358, 1987This is not a relevant population.

From: Appendix F, Excluded studies

Cover of Bacterial Meningitis and Meningococcal Septicaemia
Bacterial Meningitis and Meningococcal Septicaemia: Management of Bacterial Meningitis and Meningococcal Septicaemia in Children and Young People Younger than 16 Years in Primary and Secondary Care.
NICE Clinical Guidelines, No. 102.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2010.
Copyright © 2010, Royal College of Obstetricians and Gynaecologists.

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