Abstract
Meningococcal disease is normally suspected on clinical grounds and is confirmed by isolation of Neisseria meningitidis bacteria from blood or cerebrospinal fluid or, more recently, by serology or PCR of cerebrospinal fluid. Achieving confirmation of a clinical diagnosis of meningococcal disease has become more difficult in the last few years. The pre-hospitalization administration of parenteral benzylpenicillin normally renders blood cultures sterile, and lumbar puncture is undertaken less frequently, especially in young children. We evaluated PCR for the detection of meningococcal DNA in 80 blood samples taken from patients with known or suspected meningococcal disease or from patients with other diagnoses (negative controls). Both the sensitivity and the specificity of the test were 100% for patients with confirmed cases of meningococcal disease when the blood buffy coat was used (83 to 100% sensitivity and 87 to 100% specificity with 95% confidence limits). Positive PCR results could be obtained from both blood buffy coat and serum samples. Sensitivity was unaffected by prior antibiotic treatment. PCR is a rapid, sensitive test that may be used to confirm a diagnosis of meningococcal disease by using peripheral blood samples. Introduction of this test into clinical laboratories may in some cases obviate the need for lumbar puncture to be performed on patients with suspected meningococcal disease. Our results demonstrate that a substantial number of cases of meningococcal disease are not confirmed by conventional techniques and remain undiagnosed. If the PCR test described here was widely applied, the number of cases of meningococcal disease ascertained might rise by as much as 60% greater than that recognized at present. It is likely that we are in a prevaccination era for meningococcal disease. Better case ascertainment is urgently required to assess the need for vaccines, to determine their costs and benefits, and to monitor their efficacies.
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Selected References
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- Anderson E. L., Bowers T., Mink C. M., Kennedy D. J., Belshe R. B., Harakeh H., Pais L., Holder P., Carlone G. M. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun. 1994 Aug;62(8):3391–3395. doi: 10.1128/iai.62.8.3391-3395.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjune G., Høiby E. A., Grønnesby J. K., Arnesen O., Fredriksen J. H., Halstensen A., Holten E., Lindbak A. K., Nøkleby H., Rosenqvist E. Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet. 1991 Nov 2;338(8775):1093–1096. doi: 10.1016/0140-6736(91)91961-s. [DOI] [PubMed] [Google Scholar]
- Bohr V., Rasmussen N., Hansen B., Kjersem H., Jessen O., Johnsen N., Kristensen H. S. 875 cases of bacterial meningitis: diagnostic procedures and the impact of preadmission antibiotic therapy. Part III of a three-part series. J Infect. 1983 Nov;7(3):193–202. doi: 10.1016/s0163-4453(83)96980-3. [DOI] [PubMed] [Google Scholar]
- Boom R., Sol C. J., Salimans M. M., Jansen C. L., Wertheim-van Dillen P. M., van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1990 Mar;28(3):495–503. doi: 10.1128/jcm.28.3.495-503.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cartwright K., Reilly S., White D., Stuart J. Early treatment with parenteral penicillin in meningococcal disease. BMJ. 1992 Jul 18;305(6846):143–147. doi: 10.1136/bmj.305.6846.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight A. I., Ni H., Cartwright K. A., McFadden J. J. Identification and characterization of a novel insertion sequence, IS1106, downstream of the porA gene in B15 Neisseria meningitidis. Mol Microbiol. 1992 Jun;6(11):1565–1573. doi: 10.1111/j.1365-2958.1992.tb00878.x. [DOI] [PubMed] [Google Scholar]
- Longo M. C., Berninger M. S., Hartley J. L. Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. Gene. 1990 Sep 1;93(1):125–128. doi: 10.1016/0378-1119(90)90145-h. [DOI] [PubMed] [Google Scholar]
- Milagres L. G., Ramos S. R., Sacchi C. T., Melles C. E., Vieira V. S., Sato H., Brito G. S., Moraes J. C., Frasch C. E. Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy. Infect Immun. 1994 Oct;62(10):4419–4424. doi: 10.1128/iai.62.10.4419-4424.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ni H., Knight A. I., Cartwright K., Palmer W. H., McFadden J. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet. 1992 Dec 12;340(8833):1432–1434. doi: 10.1016/0140-6736(92)92622-m. [DOI] [PubMed] [Google Scholar]
- Richards P. G., Towu-Aghantse E. Dangers of lumbar puncture. Br Med J (Clin Res Ed) 1986 Mar 1;292(6520):605–606. doi: 10.1136/bmj.292.6520.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saukkonen K., Abdillahi H., Poolman J. T., Leinonen M. Protective efficacy of monoclonal antibodies to class 1 and class 3 outer membrane proteins of Neisseria meningitidis B:15:P1.16 in infant rat infection model: new prospects for vaccine development. Microb Pathog. 1987 Oct;3(4):261–267. doi: 10.1016/0882-4010(87)90059-3. [DOI] [PubMed] [Google Scholar]
- Van Der Ley P., Poolman J. T. Construction of a multivalent meningococcal vaccine strain based on the class 1 outer membrane protein. Infect Immun. 1992 Aug;60(8):3156–3161. doi: 10.1128/iai.60.8.3156-3161.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]