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Epidemiology of meningococcal meningitis in Belgium
Journal of Infection (1981) 3, Supplement 1, 63-70
Epidemiology of meningococcal meningitis in Belgium S. De Maeyer,* J.-M. Sebat and G. Reginstert
*Institute of Hygiene and Epidemiology, 14 rue J. Wytsman, B-1050, Brussels, Belgium and ?Institute of Hygiene and Social Medicine, University of Liege, Belgium Summary The results of a sero-cpidemiological study of an outbreak of meningococcal disease in Belgium are reported. This epidemic, which commenced in 1969, reached its peak incidence (five cases per 100000 of th6 population) in 1971 and 1972. Thereafter the incidence of disease decreased and, currently, has fallen to normal inter-epidemic proportions (one case per 100 000 of the popul~ttion p e r year). The epidemic was caused by Neisseria meningitidis serogroup B, serotype 2 being principally involved. The prevalence of serotype 2 amongst patients.fell during the transition from epidemic to non-epidemic periods, but the difference was not statistically significant. However, amongst carriers the low prevalence of this serotype decreased significantly during the transition period. Serotype 2 was thus strongly associated with this epidemic of meningococcal disease. The influence of carriage of this serotype on the incidence of clinical disease cannot be precisely determined. However, a direct relationship appears probable.
Introduction A recrudescence of meningococcal disease began in Belgium during 1969, reaching its highest incidence in 1971 and 1972 with 518 and 519 reported cases respectively (Fig. 1). The incidence of disease decreased thereafter and, at the present, the n u m b e r of notified cases is about 100 per year. This probably represents a true total of between 150 and 200 cases as undernotification is a well recognised p h e n o m e n o n . The notification rate during the peak of the epidemic was about five per 100 000 of the population and had fallen to one per 1 0 0 0 0 0 at the end of the outbreak. Serogroup B accounted for about 75 per cent of the strains isolated from patients during the outbreak, only 15-25 per cent belonging to serogroups A and C (Fig. 2). A few cases were due to serogroup W135, which was first isolated in Belgium during 1974. The 29E serogroup was also isolated from one case that year. Isolates from serogroup B were also prevalent in carriers. Nearly all such strains were sensitive to penicillins, tetracyclines, macrolides, chloramphenicol and the rifamycins. However, sulphonamide resistance was c o m m o n , especially in serogroup A isolates. As shown in Table I, a significant proportion of serogroup B and C isolates were also sulphonamide-resistant. Reprint requests to: Dr S. De Maeyer, Institute of Hygiene and Epidemiology, 14 Rue J. Wytsman, B-1050 Brussels, Belgium. 0163-4453/81/011063 + 08 $01.00/0
© 1981 The British Society for the Study of Infection
64
S. De Maeyer, J.-M. Seba and G. Reginster 520
518
519
480
440 418
4O0 360
352
32O m
o ~
280
"6
.~ 240 z
8
I
2OO 160 136 3
136\
131
120
t
8O
0
5 ,,
!,1,,,,
50
I00
e4
!
40 -
Fig. 1.
127
a
~
9
I,,,,I,,
55
60
,Jl,,,,I,~,,I
65 Year
70
75
80
Meningococcal diseases. Notified cases in Belgium.
-
90-
~
8070-
--Seroqroup
o~ 6 0 -
g g
50-
~_ 4 0 3020~
/
S
e
r
o
g
r
o
u
/--Serogroup p
C A
I0r 71
Fig. 2.
T ~ 72
7:5
,'~ J 74 75 Year
= 76
~ " " ~ 77 78
r'~ Serogroup29E 79
Serogroups of N. meningitidis isolated from patients.
Meningococcal meningitis in Belgium
65
The mode of spread of specific strains within populations is not clearly understood. Studies of transmission based on serogrouping methods alone are limited by the predominance of single groups during determined periods and geographical areas (Frasch, 1979). Subdivision of serogroups into serotypes has assisted epidemiological studies. Frasch (1979) demonstrated that serogroups B, C, Y and W135 shared several serotype determinants, whereas, other serogroups, such as A, X and 29E, had few serotypes in common with serogroups B and C (Table II). A number of specific serotypes, notably serotype 2, are particularly associated with meningococcal disease. Table I Susceptibility of Neisseria meningitidis (Belgium 1978). MIC (l~g/ml) distribution for 92 strains MIC: No. of strains susceptible to dose <6-25
12.5
25
50
>100
Serogroup A (4 strains)
4 4 4 4
Serogroup B (80 strains)
71 72 72
4 1 2
70 Serogroup C (8 strains)
7 7 7
1 1
6
1
I 3
1 2 3
4 4
1
2
7
1
Sulfadiazine Sulfamethoxazole + trimethoprim Sulfamet hoxypyridazine Sulfadiazine Sulfamethoxazole Sulfamethoxazole + trimethoprim Sulfamethoxypyridazine Sulfadiazine Sulfamethoxazole Sulfamethoxazole + trimethoprim Sulfamethoxypyridazine
I
Table II Distribution o f serotypes among meningococcai strains isolated from cases and carriers worldwide (1963-78) Serotype 1 2 4 5 6 8 9 11 12 13 14 15 NT Total
B (%) 76 198 6 12 27 62 18 12 12 3 12 25 192 655
C (%)
(11.6) 11 (30-2) 50 (0.9) 0 (1.8) 1 (4.1) 0 (9"5) 1 (2-8) 1 (1.8) 3 (1.8) 0 (0.5) 0 (1.8) 0 (3.8) 0 (29.3) 36 (100) 103
Data from Frasch (1979).
(10-7) (48.5) (1) (1) (1) (2.9)
(35) (100)
Y (%) 1 16 0 3 0 0 0 0 0 0 11 1 38 70
(7) (22.9) (4-3)
(15.7) (7) (54.3) (100)
W135 (%) 1 21 1 1 0 0 0 0 1 0 0 0 30 55
(1.8) (38.2) (1.8) (1.8)
(1-8)
(54.5) (100)
X (%)
29E (%)
0 0 0 0 0 2 0 0 1 0 5 3 10 21
4 0 0 0 0 1 2 1 1 0 3 5 10 27
(9.5) (4.8) (23.8) (14.3) (47-6) (100)
(14.8)
Total (%)
93 285 7 17 27 (3.7) 66 (7.4) 21 (3.7) 16 (3,7) 15 3 (11.1) 31 (18-5) 34 (37) 316 (100) 931
(10) (31.3) (0.7) (1.8) (2.9) (7.1) (2.3) (1-7) (1.6) (0.3) (3.3) (3.7) (33.9) (100)
66
S. De Maeyer, J.-M. Seba and G.
Reginster
Frasch and Chapman (1973) have'shown that more than 50 per cent of isolates from clinical disease are of serotype 2 (Table III). However, the relationship of this serotype to sporadic cases and outbreaks or epidemics has yet to be finally determined. The objectives of the present study were (1) to determine the serotypes responsible for the Belgian outbreaks, and (2) to compare the prevalence of these serotypes amongst carriers in both epidemic and non-epidemic periods so as to assess the possibility of increasing predominance of one serotype being predictive of an epidemic. Table
III Distribution of isolates of group B Neisseria meningitidis from patients and carriers according to serotype
Serotype 2-Associated Non 2-associated
No. of strains
Cases (%)*
Carriers (%)*
41 32
30 (73) 10 (31)
11 (27) 22 (69)
1
4
1 (25)
3 (75)
4
6
0
6 (100)
3
0
4 8 2 5 31 104
0 4 2 3 15 55
5 6 8 9 11 Non-typable Total
3 (100) (50) (100) (60) (48) (53)
4 4 0 2 16 49
(100) (50) (40) (52) (47)
*Percentage of each serotype isolated from cases and from carriers. Data from Frasch and Chapman (1973).
Methods
Two populations were investigated: (1) Carriers. In order to investigate carriage, a longitudinal study of 400 schoolchildren, aged from three to 12 years, was undertaken. These children were routinely surveyed for carriage of Neisseria meningitidis from 1974 onwards. Trans-oral rhinopharyngeal swabs were taken four to five times yearly. These swabs were inoculated directly onto Thaver-Martin medium modified by the addition of one per cent V.C.N. (Vancomycin, Colistin, Nystatin) inhibitor and the plates were incubated in a candle jar at 37°C for 24 hours. (2) Patients. Isolates were obtained from a group of children hospitalised with typical features of meningitis and from whom N. meningitidis was obtained from cerebrospinal fluid or blood culture. All presumptive isolates ofN. meningitidis were subcultured on Columbia agar enriched with sheep blood and were subsequently definitively identified by colonial morphology, oxidase and catalase reactions, and standard sugar fermentations. Isolates of N. meningitidis were thereafter serogrouped by a slide agglutination technique, using sera prepared at this laboratory or
Meningococcal meningitis in Belgium
67
obtained from the lnstitut Pasteur, and serotyped by the immunodiffusion method. Results
The iresults of serotyping of serogroup B strains in both patients with meningococcal disease and the carriage study group, in two representative years (1976 and 1979), are shown in Tables IV and V. The numbers obtained in 1974 and 1975 were insufficient for analysis. Table IV Distribution of isolates of group B Neisseria meningitidis from patients and carriers according to serotype (Belgium 1976) Serotype Type 2-associated 1 5 8 11 12 13 1.8 1.6 1.12 Total non-type 2 Non-typable Total
No. of strains 33 6 3 6 1 3 4 3 2 3 31 37 101
(32.6)
Cases (%)*
Carriers (%)*
14 (73.7) 1 0 0 0 0 0 0 0 0
19 (23) 5 3 6 1 3 4 3 2 3
1 4 19
30 33 83
*Percentage of type 2-associated isolated from cases and carriers.
Distribution of isolates of group B N e i s s e r i a m e n i n g i t i d i s from patients and carriers according to serotype (Belgium 1979)
Table V
Serotype Type 2-associated 1 1,6 1,8 4 5 6 8 11 12 13 14 15 Total non-type 2 Non-typable Total
No. of strains 88 46 5 7 7 4 4 15 1 12 4 2 8 115 110 313
Cases (%)*
55
(65)
8 0 0 0 1 0 2 0 0 3 0 2 16 13 84
*Percentage of type 2-associated isolates from cases and carriers.
Carriers (%)* 33 (14) 38 5 7 7 3 4 13 1 12 1 2 6 99 97 229
68
S. De Maeyer, J.-M. Seba and G. Reginster
Comparison of the results in 1976, the year the epidemic ended, and 1979 shows that serotype 2 was prevalent at both times of sampling. Serotype 2 accounted for 73 per cent of all group 13 strains isolated from patients in 1976 and 65 per cent in 1979. This difference is not statistically significant. Equally, there was no increase in the proportion of specific non-type 2 or non-typable strains. The prevalence of serotype 2 was lower amongst strains isolated from those members of the longitudinal study group who were found to be carriers and showed a statistically significant decrease from 1976 to 1979 (Fig. 3). Serotype 1 and associated types were shown to be increasing, but the 'carrier' group also demonstrated a much higher prevalence of non-typable strains compared to the patient group (Tables IV and V). I00
%
50
0
I 74
I 75
I 76
I 77
I 78
I 79
Year
Fig. 3.
Serotype 2 in patients (0) and in carriers (&). Discussion
Studies on the carriage rates of N. meningitidis appeared to have little value in predicting the incidence of clinical disease, possibly because of variations in virulence within specific serogroups. The factors determining virulence of meningococci are not fully understood but may be associated with the capsule and capsular polysaccharides, lipopolysaccharides, outer membrane proteins and fimbriae. Serotyping of meningococcal serogroups allows the types responsible for disease to be identified. Serotype 2 has been recognised as prevalent during epidemic periods in various countries including the United States (Frasch and Chapman, 1973), Belgium, England (Jones and Tobin, 1976) and Spain
Meningococcal meningitis in Belgium
69
(Saez-Nieto, Fenoll and Casal, personal communication). However, in Nor~¢ay serotype 15 is a frequent pathogen. Less data are available concerning non-epidemic periods. Recently, Craven, Frasch, Mocca, Rose and Gonzalez (1979), whilst investigating a disease-free military population, observed that the prevalence of serotype 2 was very low. Amongst isolates of serogroup B it represented less than four per cent. However this study was characterised by a high proportion (76 per cent) of untypable strains. A further study in the United States (Broud, Griffis and Baker, 1979) demonstrated that, in contrast to epidemics, sporadic meningococcal disease was caused by a variety of differing serotypes and concluded that a serotype specific vaccine might be an unsatisfactory preventative measure. In Belgium, the prevalence of serotype 2 in patients decreased from epidemic to non-epidemic periods, but this decrease was not statistically significant. Further, the heterogenicity of serotypes prevalent in interepidemic periods commented on by Broud, Griffis and Baker (1979) was not observed. A variety of differences between the Belgian and American study populations could explain this disparity. The lower prevalence of serotype 2 amongst carriers is in accordance with previous observations (Frasch and Chapman, 1973). In Belgium, the prevalence of this serotype decreased from epidemic to non-epidemic periods, possibly predicting a future decrease in incidence of serotype 2 amongst patients. The next most common serotype (after serotype 2) was serotype 1 (and associated types). Particular attention should perhaps be paid to this serotype, which, in 1979, represented eight per cent of isolates from patients, and which might in the future fill the epidemiological gap vacated by serotype 2. In conclusion, it is apparent that serotype 2 was closely associated Witfi -a recent recrudescence of epidemic meningococcal disease in Belgium and that its predominance has so far continued into a non-epidemic period. It is, perhaps, too early to determine exactly the role of carriage in the influence of this serotype, but its distribution amongst carriers is probably directly related to the epidemiological situation. (We thank Dr C. E. Frasch for his scientific help during this study, Mrs Van Vliet for the statistical analysis of the results and Dr A. Noel for the medical supervision of the schoolchildren. This work was supported by a grant from the Fond de la Recherche Scientifique M6dicale Researchnr. 3.9005.75.) References
Broud, D. D., Griffis, J. M. and Baker C. J. (1979). Heterogeneity of serotypes of Neisseria meningitidis that cause endemic disease. The Journal oflnfectious Diseases, 140, 465. Craven, D. A., Frasch, C. E., Mocca, L. F., Rose, F. B. and Gonzalez, R. (1979). Rapid serogroup identificationofNeisseria meningitidis by using antiserum agar. Prevalence of serogroups in a disease-free military population. The Journal of Clinical Microbiology, 10, 302.
70
S. De Maeyer, ,I.-M. Seba and G. Reginster
Frasch, C. E. and Chapman, S. S. (1973). Classification ofN. meningitidis group B into distinct serotypes. The Journal of lnfectious Diseases, 127, 149. Frasch, C. E. Non capsular surface antigens of N. meningitidis. Seminars in Infectious Disease. Stratton Intercontinental Medical Book Corporation, New York (1979), pp. 304-337. Jones, D. M. and Tobin, B. M. (1976). Serotypes of group B meningococci. The Journal of Clinical Pathology, 29, 746. Reginster, G., Seba, J. M. and De Maeyer, S. (1979). Serotypage des souches de N. meningitidis serogroupe B isol6es en Belgique. Microbia, 5, 3. Saez-Nieto, J. A., Fenoll, A. and Casal, J. (1978). Serotypes of group B and C meningococci in Spain (Personal Communication).
Epidemiology of meningococcal meningitis in Belgium S. De Maeyer,* J.-M. Sebat and G. Reginstert
*Institute of Hygiene and Epidemiology, 14 rue J. Wytsman, B-1050, Brussels, Belgium and ?Institute of Hygiene and Social Medicine, University of Liege, Belgium Summary The results of a sero-cpidemiological study of an outbreak of meningococcal disease in Belgium are reported. This epidemic, which commenced in 1969, reached its peak incidence (five cases per 100000 of th6 population) in 1971 and 1972. Thereafter the incidence of disease decreased and, currently, has fallen to normal inter-epidemic proportions (one case per 100 000 of the popul~ttion p e r year). The epidemic was caused by Neisseria meningitidis serogroup B, serotype 2 being principally involved. The prevalence of serotype 2 amongst patients.fell during the transition from epidemic to non-epidemic periods, but the difference was not statistically significant. However, amongst carriers the low prevalence of this serotype decreased significantly during the transition period. Serotype 2 was thus strongly associated with this epidemic of meningococcal disease. The influence of carriage of this serotype on the incidence of clinical disease cannot be precisely determined. However, a direct relationship appears probable.
Introduction A recrudescence of meningococcal disease began in Belgium during 1969, reaching its highest incidence in 1971 and 1972 with 518 and 519 reported cases respectively (Fig. 1). The incidence of disease decreased thereafter and, at the present, the n u m b e r of notified cases is about 100 per year. This probably represents a true total of between 150 and 200 cases as undernotification is a well recognised p h e n o m e n o n . The notification rate during the peak of the epidemic was about five per 100 000 of the population and had fallen to one per 1 0 0 0 0 0 at the end of the outbreak. Serogroup B accounted for about 75 per cent of the strains isolated from patients during the outbreak, only 15-25 per cent belonging to serogroups A and C (Fig. 2). A few cases were due to serogroup W135, which was first isolated in Belgium during 1974. The 29E serogroup was also isolated from one case that year. Isolates from serogroup B were also prevalent in carriers. Nearly all such strains were sensitive to penicillins, tetracyclines, macrolides, chloramphenicol and the rifamycins. However, sulphonamide resistance was c o m m o n , especially in serogroup A isolates. As shown in Table I, a significant proportion of serogroup B and C isolates were also sulphonamide-resistant. Reprint requests to: Dr S. De Maeyer, Institute of Hygiene and Epidemiology, 14 Rue J. Wytsman, B-1050 Brussels, Belgium. 0163-4453/81/011063 + 08 $01.00/0
© 1981 The British Society for the Study of Infection
64
S. De Maeyer, J.-M. Seba and G. Reginster 520
518
519
480
440 418
4O0 360
352
32O m
o ~
280
"6
.~ 240 z
8
I
2OO 160 136 3
136\
131
120
t
8O
0
5 ,,
!,1,,,,
50
I00
e4
!
40 -
Fig. 1.
127
a
~
9
I,,,,I,,
55
60
,Jl,,,,I,~,,I
65 Year
70
75
80
Meningococcal diseases. Notified cases in Belgium.
-
90-
~
8070-
--Seroqroup
o~ 6 0 -
g g
50-
~_ 4 0 3020~
/
S
e
r
o
g
r
o
u
/--Serogroup p
C A
I0r 71
Fig. 2.
T ~ 72
7:5
,'~ J 74 75 Year
= 76
~ " " ~ 77 78
r'~ Serogroup29E 79
Serogroups of N. meningitidis isolated from patients.
Meningococcal meningitis in Belgium
65
The mode of spread of specific strains within populations is not clearly understood. Studies of transmission based on serogrouping methods alone are limited by the predominance of single groups during determined periods and geographical areas (Frasch, 1979). Subdivision of serogroups into serotypes has assisted epidemiological studies. Frasch (1979) demonstrated that serogroups B, C, Y and W135 shared several serotype determinants, whereas, other serogroups, such as A, X and 29E, had few serotypes in common with serogroups B and C (Table II). A number of specific serotypes, notably serotype 2, are particularly associated with meningococcal disease. Table I Susceptibility of Neisseria meningitidis (Belgium 1978). MIC (l~g/ml) distribution for 92 strains MIC: No. of strains susceptible to dose <6-25
12.5
25
50
>100
Serogroup A (4 strains)
4 4 4 4
Serogroup B (80 strains)
71 72 72
4 1 2
70 Serogroup C (8 strains)
7 7 7
1 1
6
1
I 3
1 2 3
4 4
1
2
7
1
Sulfadiazine Sulfamethoxazole + trimethoprim Sulfamet hoxypyridazine Sulfadiazine Sulfamethoxazole Sulfamethoxazole + trimethoprim Sulfamethoxypyridazine Sulfadiazine Sulfamethoxazole Sulfamethoxazole + trimethoprim Sulfamethoxypyridazine
I
Table II Distribution o f serotypes among meningococcai strains isolated from cases and carriers worldwide (1963-78) Serotype 1 2 4 5 6 8 9 11 12 13 14 15 NT Total
B (%) 76 198 6 12 27 62 18 12 12 3 12 25 192 655
C (%)
(11.6) 11 (30-2) 50 (0.9) 0 (1.8) 1 (4.1) 0 (9"5) 1 (2-8) 1 (1.8) 3 (1.8) 0 (0.5) 0 (1.8) 0 (3.8) 0 (29.3) 36 (100) 103
Data from Frasch (1979).
(10-7) (48.5) (1) (1) (1) (2.9)
(35) (100)
Y (%) 1 16 0 3 0 0 0 0 0 0 11 1 38 70
(7) (22.9) (4-3)
(15.7) (7) (54.3) (100)
W135 (%) 1 21 1 1 0 0 0 0 1 0 0 0 30 55
(1.8) (38.2) (1.8) (1.8)
(1-8)
(54.5) (100)
X (%)
29E (%)
0 0 0 0 0 2 0 0 1 0 5 3 10 21
4 0 0 0 0 1 2 1 1 0 3 5 10 27
(9.5) (4.8) (23.8) (14.3) (47-6) (100)
(14.8)
Total (%)
93 285 7 17 27 (3.7) 66 (7.4) 21 (3.7) 16 (3,7) 15 3 (11.1) 31 (18-5) 34 (37) 316 (100) 931
(10) (31.3) (0.7) (1.8) (2.9) (7.1) (2.3) (1-7) (1.6) (0.3) (3.3) (3.7) (33.9) (100)
66
S. De Maeyer, J.-M. Seba and G.
Reginster
Frasch and Chapman (1973) have'shown that more than 50 per cent of isolates from clinical disease are of serotype 2 (Table III). However, the relationship of this serotype to sporadic cases and outbreaks or epidemics has yet to be finally determined. The objectives of the present study were (1) to determine the serotypes responsible for the Belgian outbreaks, and (2) to compare the prevalence of these serotypes amongst carriers in both epidemic and non-epidemic periods so as to assess the possibility of increasing predominance of one serotype being predictive of an epidemic. Table
III Distribution of isolates of group B Neisseria meningitidis from patients and carriers according to serotype
Serotype 2-Associated Non 2-associated
No. of strains
Cases (%)*
Carriers (%)*
41 32
30 (73) 10 (31)
11 (27) 22 (69)
1
4
1 (25)
3 (75)
4
6
0
6 (100)
3
0
4 8 2 5 31 104
0 4 2 3 15 55
5 6 8 9 11 Non-typable Total
3 (100) (50) (100) (60) (48) (53)
4 4 0 2 16 49
(100) (50) (40) (52) (47)
*Percentage of each serotype isolated from cases and from carriers. Data from Frasch and Chapman (1973).
Methods
Two populations were investigated: (1) Carriers. In order to investigate carriage, a longitudinal study of 400 schoolchildren, aged from three to 12 years, was undertaken. These children were routinely surveyed for carriage of Neisseria meningitidis from 1974 onwards. Trans-oral rhinopharyngeal swabs were taken four to five times yearly. These swabs were inoculated directly onto Thaver-Martin medium modified by the addition of one per cent V.C.N. (Vancomycin, Colistin, Nystatin) inhibitor and the plates were incubated in a candle jar at 37°C for 24 hours. (2) Patients. Isolates were obtained from a group of children hospitalised with typical features of meningitis and from whom N. meningitidis was obtained from cerebrospinal fluid or blood culture. All presumptive isolates ofN. meningitidis were subcultured on Columbia agar enriched with sheep blood and were subsequently definitively identified by colonial morphology, oxidase and catalase reactions, and standard sugar fermentations. Isolates of N. meningitidis were thereafter serogrouped by a slide agglutination technique, using sera prepared at this laboratory or
Meningococcal meningitis in Belgium
67
obtained from the lnstitut Pasteur, and serotyped by the immunodiffusion method. Results
The iresults of serotyping of serogroup B strains in both patients with meningococcal disease and the carriage study group, in two representative years (1976 and 1979), are shown in Tables IV and V. The numbers obtained in 1974 and 1975 were insufficient for analysis. Table IV Distribution of isolates of group B Neisseria meningitidis from patients and carriers according to serotype (Belgium 1976) Serotype Type 2-associated 1 5 8 11 12 13 1.8 1.6 1.12 Total non-type 2 Non-typable Total
No. of strains 33 6 3 6 1 3 4 3 2 3 31 37 101
(32.6)
Cases (%)*
Carriers (%)*
14 (73.7) 1 0 0 0 0 0 0 0 0
19 (23) 5 3 6 1 3 4 3 2 3
1 4 19
30 33 83
*Percentage of type 2-associated isolated from cases and carriers.
Distribution of isolates of group B N e i s s e r i a m e n i n g i t i d i s from patients and carriers according to serotype (Belgium 1979)
Table V
Serotype Type 2-associated 1 1,6 1,8 4 5 6 8 11 12 13 14 15 Total non-type 2 Non-typable Total
No. of strains 88 46 5 7 7 4 4 15 1 12 4 2 8 115 110 313
Cases (%)*
55
(65)
8 0 0 0 1 0 2 0 0 3 0 2 16 13 84
*Percentage of type 2-associated isolates from cases and carriers.
Carriers (%)* 33 (14) 38 5 7 7 3 4 13 1 12 1 2 6 99 97 229
68
S. De Maeyer, J.-M. Seba and G. Reginster
Comparison of the results in 1976, the year the epidemic ended, and 1979 shows that serotype 2 was prevalent at both times of sampling. Serotype 2 accounted for 73 per cent of all group 13 strains isolated from patients in 1976 and 65 per cent in 1979. This difference is not statistically significant. Equally, there was no increase in the proportion of specific non-type 2 or non-typable strains. The prevalence of serotype 2 was lower amongst strains isolated from those members of the longitudinal study group who were found to be carriers and showed a statistically significant decrease from 1976 to 1979 (Fig. 3). Serotype 1 and associated types were shown to be increasing, but the 'carrier' group also demonstrated a much higher prevalence of non-typable strains compared to the patient group (Tables IV and V). I00
%
50
0
I 74
I 75
I 76
I 77
I 78
I 79
Year
Fig. 3.
Serotype 2 in patients (0) and in carriers (&). Discussion
Studies on the carriage rates of N. meningitidis appeared to have little value in predicting the incidence of clinical disease, possibly because of variations in virulence within specific serogroups. The factors determining virulence of meningococci are not fully understood but may be associated with the capsule and capsular polysaccharides, lipopolysaccharides, outer membrane proteins and fimbriae. Serotyping of meningococcal serogroups allows the types responsible for disease to be identified. Serotype 2 has been recognised as prevalent during epidemic periods in various countries including the United States (Frasch and Chapman, 1973), Belgium, England (Jones and Tobin, 1976) and Spain
Meningococcal meningitis in Belgium
69
(Saez-Nieto, Fenoll and Casal, personal communication). However, in Nor~¢ay serotype 15 is a frequent pathogen. Less data are available concerning non-epidemic periods. Recently, Craven, Frasch, Mocca, Rose and Gonzalez (1979), whilst investigating a disease-free military population, observed that the prevalence of serotype 2 was very low. Amongst isolates of serogroup B it represented less than four per cent. However this study was characterised by a high proportion (76 per cent) of untypable strains. A further study in the United States (Broud, Griffis and Baker, 1979) demonstrated that, in contrast to epidemics, sporadic meningococcal disease was caused by a variety of differing serotypes and concluded that a serotype specific vaccine might be an unsatisfactory preventative measure. In Belgium, the prevalence of serotype 2 in patients decreased from epidemic to non-epidemic periods, but this decrease was not statistically significant. Further, the heterogenicity of serotypes prevalent in interepidemic periods commented on by Broud, Griffis and Baker (1979) was not observed. A variety of differences between the Belgian and American study populations could explain this disparity. The lower prevalence of serotype 2 amongst carriers is in accordance with previous observations (Frasch and Chapman, 1973). In Belgium, the prevalence of this serotype decreased from epidemic to non-epidemic periods, possibly predicting a future decrease in incidence of serotype 2 amongst patients. The next most common serotype (after serotype 2) was serotype 1 (and associated types). Particular attention should perhaps be paid to this serotype, which, in 1979, represented eight per cent of isolates from patients, and which might in the future fill the epidemiological gap vacated by serotype 2. In conclusion, it is apparent that serotype 2 was closely associated Witfi -a recent recrudescence of epidemic meningococcal disease in Belgium and that its predominance has so far continued into a non-epidemic period. It is, perhaps, too early to determine exactly the role of carriage in the influence of this serotype, but its distribution amongst carriers is probably directly related to the epidemiological situation. (We thank Dr C. E. Frasch for his scientific help during this study, Mrs Van Vliet for the statistical analysis of the results and Dr A. Noel for the medical supervision of the schoolchildren. This work was supported by a grant from the Fond de la Recherche Scientifique M6dicale Researchnr. 3.9005.75.) References
Broud, D. D., Griffis, J. M. and Baker C. J. (1979). Heterogeneity of serotypes of Neisseria meningitidis that cause endemic disease. The Journal oflnfectious Diseases, 140, 465. Craven, D. A., Frasch, C. E., Mocca, L. F., Rose, F. B. and Gonzalez, R. (1979). Rapid serogroup identificationofNeisseria meningitidis by using antiserum agar. Prevalence of serogroups in a disease-free military population. The Journal of Clinical Microbiology, 10, 302.
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Frasch, C. E. and Chapman, S. S. (1973). Classification ofN. meningitidis group B into distinct serotypes. The Journal of lnfectious Diseases, 127, 149. Frasch, C. E. Non capsular surface antigens of N. meningitidis. Seminars in Infectious Disease. Stratton Intercontinental Medical Book Corporation, New York (1979), pp. 304-337. Jones, D. M. and Tobin, B. M. (1976). Serotypes of group B meningococci. The Journal of Clinical Pathology, 29, 746. Reginster, G., Seba, J. M. and De Maeyer, S. (1979). Serotypage des souches de N. meningitidis serogroupe B isol6es en Belgique. Microbia, 5, 3. Saez-Nieto, J. A., Fenoll, A. and Casal, J. (1978). Serotypes of group B and C meningococci in Spain (Personal Communication).