Impact of meningococcal vaccination with combined serogroups A and C polysaccharide vaccine on carriage of Neisseria meningitidis C

Population and selection of sample.
On the basis of meningococcal disease incidence for the 1995/1996 epidemiological year (week 41, 1995 to week 40, 1996), the pre-vaccination study conducted from December 1996 to January 1997 identified two geographical areas in Galicia, Spain, which were duly denominated high- and low-incidence areas. The study population was selected from one administrative zone in each of these geographical areas, and a stratified two-stage design was then used to obtain the respective pre-vaccination samples in the population aged 219 years (Fernández et al., 1999).

In the study conducted 1 year after vaccination (1998), with the same geographical areas and individuals, the age range was 519 years. The 24 year age group was not included in this second study, owing to the fact that the prevalence of serogroup C carriers reported by the pre-vaccination study was very low and that the possibility of finding differences between the two studies was therefore judged negligible.

Prevalences were calculated with the aid of a ratio estimator, and 95 % confidence intervals obtained. To compare the prevalences reported by the two studies, the variance of the estimators was estimated using the delta method, and a normal-distribution test applied. The samples were weighted to compensate for the different selection probabilities, and the complexity of the design thereby incorporated into the data analysis.

Specimen collection and analysis.
Nasopharyngeal specimens were collected by trained staff, plated on ThayerMartin agar (Oxoid) and, after incubation in 5 % CO₂ at 37 °C for 24 h at regional laboratories, sent to the National Reference Laboratory in Majadahonda, Madrid, Spain, for isolation and identification of strains. Serosubtyping N. meningitidis serogroup C was done under the above-described conditions (Fernández et al., 1999).

The approximate total population of 519-year-old Galicians is 505 483. The pre-vaccination study analysed 8727 specimens. Prevalence of N. meningitidis serogroup C carriers was 1.51 % (95 % CI, 0.922.11) in the meningococcal disease high-incidence area and 0.94 % (95 % CI, 0.141.74) in the low-incidence area. The meningococcal group A and C polysaccharide vaccination campaign achieved an overall vaccination coverage of 85.02 %, ranging from over 90 % in the 59 and 1014 age groups to around 60 % in the 1519 age group.

In the post-vaccination study, a total of 5742 specimens was obtained. Prevalence of N. meningitidis serogroup C carriers was now 0.79 % (95 % CI, 0.451.13) in the meningococcal disease high-incidence area and 0.32 % (95 % CI, 0.040.60) in the low-incidence area. The percentage decline observed in prevalence of N. meningitidis C was thus 47 % in the high and 65 % in the low-incidence areas. Table 1 shows these results for both studies, with the respective carriage prevalences of N. meningitidis serogroup B and C : 2b : P1.2.5 strains for the two incidence areas. The prevalence of other serogroups and non-groupable strains is likewise shown. While the N. meningitidis B carriage rate also declined, it was only the decrease in N. meningitidis C carriers in the high-incidence area that proved statistically significant (P = 0.03). A statistically significant rise in the carriage rate for other serogroups and non-groupable strains was in evidence in the meningococcal disease high-incidence area. Shown also in Table 1 are the P-values for the differences observed between the studies in the two areas.

Table 1.N. meningitidis carriage rates and p-values for differences in each area

A breakdown of serogroup C carriers by age group is depicted in Fig. 1. There was a post-vaccination decline in prevalence of carriers aged 1014 and 1519 years in both areas. With the single exception of those in the 1519 age group in the high-incidence area, the relative decline in all these age groups exceeded 70 %. A slight rise of around 20 % in the 59 age group was also noted.

(15K): [in this window] [in a new window] Fig. 1. Pre- (solid bars) and post- (open bars) vaccination N. meningitidis serogroup C carriage rates by age group and area.

In view of the importance of the carrier state in meningococcal disease (Broome, 1986), the effect of meningococcal group A and C polysaccharide vaccine on carrier state has long been regarded as an aspect which merits proper prospective study in the context of meningococcal disease epidemiology (Gotschlich et al., 1969). Although other N. meningitidis C carrier studies have also reported a decline in carriage rates, over different periods of time, following vaccination with polysaccharide vaccine (Gotschlich et al., 1969; Stroffolini et al., 1990; Di Martino et al., 1990; Neal et al., 1998), we nevertheless feel that the high number of specimens analysed renders the data yielded by our study of considerable interest.

The decrease in carriers observed among the 1014 and 1519 age groups is similar to that observed by Neal et al. (1998), yet in this latter study subjects received chemoprophylaxis in addition to vaccine, a factor which could be expected to exert an effect on the reduction in carriers. The slight rise in prevalence observed in the 59-year-olds could, in part, be explained by the attenuated effect that polysaccharide vaccine has among the youngest age groups.

Furthermore, the results display no increase in the N. meningitidis B carriage rate 1 year after vaccination, which might mean that in this period of time serogroup B had failed to replace serogroup C in the asymptomatic nasopharyngeal carriers. The increase in the percentage of non-groupable strains was not the result of down-regulation of capsular expression; genogrouping of these strains by PCR (data not shown) showed a similar proportion of B and C serogroups to the percentage found by conventional methods. Therefore, serogroup C was not over-represented in these non-groupable isolates.

Finally, we feel that, while the effect of the natural evolution of meningococcal infection on carrier state cannot be ruled out, the results of our study must be taken to support the effect of polysaccharide vaccination on N. meningitidis C carrier state, since 1 year after vaccination the decline in prevalence was not only statistically significant but indeed coincided with the decline in disease incidence in the oldest groups among which the effect of vaccination is most marked. In 1996, 1997 and 1998, serogroup C meningococcal disease registered a downward trend, with rates of 14.04, 3.63 and 0.79 cases per 100 000 population, respectively. Broken down by age group, disease incidence declined by 79 % in the 59 age group, 91 % in the 1014 age group and 67 % in the 1519 age group.

The authors wish to thank the Galician regional team of epidemiologists and all Neisseria Reference Laboratory staff for their assistance in specimen collection and analysis.

Footnotes

Abbreviation: CI, confidence interval.