Measurement of Antibodies against Meningococcal Capsular Polysaccharides B and C in Enzyme-Linked Immunosorbent Assays: Towards an Improved Surveillance of

In order to improve the surveillance of serogroup B and C meningococcal diseases, enzyme-linked immunosorbent assays (ELISAs) specific for anti-B immunoglobulin M (IgM) and anti-C IgM and IgG antibodies were developed. The tests were evaluated by using paired sera from 122 patients with and 101 patients without laboratory evidence of meningococcal disease. Fifty-three of 67 patients (79%) with culture-confirmed serogroup B disease had an anti-B IgM antibody response; anti-B IgM levels waned rapidly in children 4 years of age had intermediate anti-B IgM titers. In contrast, only 1 and 5% of these patients had intermediate titers of anti-C IgM and anti-C IgG, respectively. The ELISAs were shown to be powerful tools for discriminating between serogroup B and C diseases in 96 to 100% of cultureconfirmed cases. For 90% of patients with culture-negative meningococcal disease, a serogroup-specific diagnosis could be established by examination of paired sera in the ELISAs. As serogroup B and C meningococci account for practically all cases of meningococcal disease in industrialized countries, the availability of these tests may improve surveillance and prevention. Meningitis and septicemia due to Neisseria meningitidis remain a major health problem worldwide (24). Serogroup B and C meningococci account for practically all cases of meningococcal disease in Europe (5) and North America (15). Since 1986, Denmark has had a high annual incidence of meningococcal disease compared with most other European countries, and in Denmark, approximately 80% of the notified cases were confirmed by culture of N. meningitidis (13, 23). Preadmission antibiotic treatment of patients suspected of meningococcal disease, which is recommended by health authorities in several countries, remains a matter of debate (2, 26). In cases of preadmission treatment, noncultural diagnostic methods, such as PCR, antigen detection, and specific antibody determination, become important tools in achieving a diagnosis; during the last 5 to 10 years, an increasing proportion of the culture-negative cases in Denmark have been confirmed by a meningococcal antibody test (MAT) (27). Antibodies towards the capsular polysaccharides are not detected in the MAT; a serological test capable of identifying serogroup B- and Cspecific antibodies would improve epidemiological surveillance. Although the purified B polysaccharide seems to be weakly immunogenic in humans and the C polysaccharide vaccine is effective only in children $2 years of age (21), specific immune responses towards the respective polysaccharides have been observed in the majority of adults and 30% of children recovering from serogroup B meningococcal disease (12) and in the majority of patients recovering from serogroup C disease (12, 16). Whether it is possible to establish a definitive serogroupspecific diagnosis and thus discriminate between serogroup B and C meningococcal diseases on the basis of the presence of specific anticapsular antibodies has been elucidated only to a limited extent (14). The aim of this study was to develop assays based on the enzyme-linked immunosorbent assay (ELISA) principle for detection of immunoglobulin M (IgM) and IgG antibodies against the meningococcal capsular polysaccharides B and C and to evaluate the assays by testing paired sera from patients with and without meningococcal disease. In preliminary experiments, the anti-B IgG assay did not detect any antibodies in sera from patients recovering from serogroup B meningococcal disease; therefore, this assay was not further developed.