Age-related immunogenicity of meningococcal polysaccharide vaccine in aboriginal children and adolescents living in a Northern Manitoba reserve community.
OBJECTIVE: To determine the total and functional serogroup C antibody response to a quadrivalent meningococcal polysaccharide vaccine in a group of aboriginal infants, children and adolescents. A secondary objective was to determine their prevalence of meningococcal carriage. DESIGN: Open prospective, before and after intervention study. SUBJECTS: Aboriginal children ages 0.5 to 19.9 years, living in a single Northern community and eligible for a public health immunization campaign conducted in all Manitoba native reserve communities to control a meningococcal serogroup C, electrophoretic type (ET) 15 outbreak. No outbreak cases had occurred in the community at the time of the study. METHODS: Total serogroup C capsular polysaccharide antibody (CPA) and functional bactericidal antibody (BA) responses were measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: Neisseria meningitidis was recovered from the oropharynx of 13 (5.2%) of 249 aboriginal children including 4 (1.6%) serogroup C isolates, all with the designation C:2a:P1.2,5 ET15. Paired sera from 152 children were available for assay. For CPA the geometric mean concentrations and proportions with > or =2 microg/ml before and after immunization were 0.69, 18% and 12.3, 96%, respectively. A significant increase in serum CPA was achieved by children of all ages, with the greatest response occurring after age 11 years. Among infants or =2 microg/ml. For BA the pre- and post-vaccine geometric mean titers were 1.02 and 45.9. The response was significantly associated with age. BA titers > or =1:8 were present, before and after immunization, respectively, in 0 and 0% of infants or =2-year-olds. CONCLUSION: The age-related total and functional group C meningococcal antibody response after quadrivalent polysaccharide vaccine among aboriginals is similar to that reported for Caucasian children. After age 2 all children made excellent CPA and BA responses. In the younger age groups the BA response was blunted but 82 to 95% achieved CPA titers of > or =2 microg/ml.
Département des sciences de la santé communautaire, Université de Sherbrooke, 3001 12th Ave N, Sherbrooke, Quebec, Canada J1H 5N4. pdewals@courrier.usherb.ca
An outbreak of meningococcal disease in Quebec province prompted a mass immunization program. The impact of this campaign on the epidemiology of meningococcal disease has not been studied.
To study the impact of a mass immunization campaign using polysaccharide vaccine on the epidemiology of meningococcal disease (MCD) and to assess serogroup C vaccine effectiveness (VE).
Analysis of MCD cases reported in Quebec from 1990 to 1998, before and after the mass immunization campaign was conducted during the winter of 1992-1993, when 84% of residents aged 6 months to 20 years (the target population, approximately 1.9 million individuals) were vaccinated.
Incidence of MCD in 1990-1998; incidence of culture-proven serogroup C MCD between April 1, 1993, and March 31, 1998, compared among vaccinated and unvaccinated persons in the target population.
The incidence of serogroup C disease decreased after the mass immunization campaign, from 1.4 per 100 000 in 1990-1992 to 0.3 per 100 000 in 1993-1998, and the overall incidence of other serogroups remained stable at 0.7 per 100 000, with a small increase in the proportion of cases caused by serogroup Y (P =.009). Protection from serogroup C MCD was indicated in the first 2 years after vaccine administration (VE, 65%; 95% confidence interval [CI], 20%-84%), but not in the next 3 years (VE, 0%; 95% CI, -5% to 65%). Vaccine effectiveness was strongly related to age at vaccination: 83% (95% CI, 39%-96%) for ages 15 through 20 years, 75% (95% CI, - 17% to 93%) for ages 10 through 14 years, and 41% (95% CI, -106% to 79%) for ages 2 through 9 years. There was no evidence of protection in children younger than 2 years; all 8 MCD cases in this age group occurred in vaccinees.
Serogroup C polysaccharide vaccine is effective for controlling outbreaks in teenaged individuals but should not be used in children younger than 2 years. The mass campaign did not induce significant serogroup switching.
Notes
Comment In: JAMA. 2001 Mar 28;285(12):1578-911268264
An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains. Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates. The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world. All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway. A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction. Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively. Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a. Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c. Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone.
Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P
Measurement of antibodies against meningococcal capsular polysaccharides B and C in enzyme-linked immunosorbent assays: towards an improved surveillance of meningococcal disease.
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 culture-confirmed 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.
Meningococcal disease continues to occur in most parts of Canada at endemic levels, with minor fluctuations. The incidence in general has changed very little over the past three decades. It is primarily a childhood infection, occurring most commonly among infants less than 1 year of age. In 1987 the risk of infection among infants in that age group was 4 times and among those aged 1 to 4 years 2.5 times that of the general population. The most susceptible appear to be infants about 3 months of age. The annual CFRs had exceeded 50% before the antibiotic era, but with early diagnosis, modern therapy and supportive measures they have been less than 10%. A revised form for reporting cases, currently being considered by provincial epidemiologists across Canada, could help to provide more clinical and epidemiologic information.
Meningococcal meningitis and septicemia are a persistent public health concern owing to the associated mortality and devastating long-term sequelae. People of all ages may be affected, with the disease burden being higher in at-risk groups. Vaccination is the most rational approach to the prevention of invasive meningococcal disease. A novel quadrivalent meningococcal (Men) serogroup A, C, W-135 and Y polysaccharide-protein conjugate vaccine (MenACWY-CRM), has recently been licensed for use in individuals aged at least 11 years old in the USA, Canada and Europe. One dose of MenACWY-CRM is well tolerated, and induces robust immunity to all constituent vaccine serogroups in 11-65 year old individuals. MenACWY-CRM was found to be noninferior to the quadrivalent meningococcal ACWY-diphtheria toxoid glycoconjugate vaccine, which is also licensed in the USA and Canada. In Europe, MenACWY-CRM is the first quadrivalent meningococcal glycoconjugate vaccine available to provide broader protection against Neisseria meningitidis serogroups A, C, W-135 and Y.
Congenital complement deficiency states occur very rarely. These deficiencies are associated with a high risk of meningococcal disease (MD). We suggest that the following groups of individuals with MD are examined for complement deficiencies: 1. Individuals belonging to families, in which more than one case of MD has occurred with an interval exceeding one month. 2. Individuals infected with the low-virulent meningococcal serogroups W-135, 29E, X, Y, Z. 3. Individuals with recurrent MD. Since properdin deficiency probably is the most common deficiency associated with MD it is important that the screening includes the alternative complement pathway.
In September 1981 a soldier died from meningococcal septicemia in a military camp in Mid-Norway. Soon afterwards one of his room-mates was transferred to a military camp in Northern-Norway where he shared sleeping quarters (room 7D) with 5 other soldiers of whom 2 fell ill with meningococcal disease 1 month later. Throat cultures were obtained from all 128 soldiers at the military camp in Northern-Norway; 41 (32%) harboured meningococci in their throats. The 3 invasive isolates and the isolates from the 4 healthy carriers at room 7D were all group B and type 15 meningococci. However, by DNA fingerprinting we could identify at least 2, probably 3, different individual strains among these 7 isolates. None of these strains were isolated from soldiers outside room 7D. By use of a B15 whole-bacterium ELISA method we showed that the levels of antimeningococcal IgG antibodies in the sera of the two cases at room 7D were low (18 and 28 OD units) compared with the mean IgG levels in the sera of their 4 healthy room mates (1150 OD units) and the mean IgG in the sera from all healthy soldiers (472 OD units).
