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Home Eurosurveillance Monthly Release  1997: Volume 2/ Issue 10 Article 1
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Eurosurveillance, Volume 2, Issue 10, 01 October 1997
Research Articles
Recent changes in meningococcal disease in Europe

Citation style for this article: Hubert B, Caugant DA. Recent changes in meningococcal disease in Europe. Euro Surveill. 1997;2(10):pii=145. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=145
B. Hubert1, D.A. Caugant2
1 Réseau National de Santé Publique, Saint-Maurice, France
2 WHO Collaborating Centre for Reference and Research on Meningococci, Oslo, Norway

Few infections can cause the social stress that occurs when meningococcal disease enters a community. The ability of Neisseria meningitidis to kill a healthy child within a few hours is one reason for this fear. It is also clear that preventive measures against this disease are limited and that they rely mainly on early management of patients and prevention of secondary cases.

N. meningitidis causes endemic and epidemic disease, but epidemics occur more frequently in developing than in industrialised countries. The development of phenotyping and genotyping methods has contributed to a better understanding of the epidemiology of meningococcal disease. Meningococci are classified into serogroups, serotypes, and subtypes on the basis of antigenic differences in their capsular polysaccharides, class 2/3 and class 1 outer membrane proteins, respectively. The characterisation of the chromosomal genotype of N. meningitidis by multilocus enzyme electrophoresis (MEE) has proved to be a more powerful tool for studying the epidemiology of the disease (1). As has been shown in the Netherlands, in the course of a few years a meningococcal clone may change serotype or subtype as a result of frequent exchange of genetic material between clones (2). The occurrence of these recombination events led to the concept of clone-complexes, which represent a group of distinct clones that are sufficiently genetically closely related to allow the recognition of a common origin.

Short-term immunity to meningococcal infection due to serogroups A, C, Y, and W135 can be obtained by vaccination with polysaccharide preparations. Vaccination is not recommended for routine immunisation of the general population for a number of reasons:

1) the vaccine has a short duration of protection (3 years) and is poorly immunogenic in children <18 months of age who represent about 25% of all cases;

2) the incidence of meningococcal disease is relatively low in most industrialised countries, ranging between 1 and 3 cases per 100 000 population per year, rates considered as the usual baseline between epidemics ;

3) the vaccine lacks a serogroup B component and meningococci of serogroup B have caused the majority of cases in the 1980s in Europe and in North America.

Conjugate vaccines against meningococci of serogroups A and C and outer membrane protein vaccines against several serogroup B meningococci are being developed to solve these problems.

The epidemiological situation is also changing in some industrialised countries. In the early 1990s, an increased incidence associated with the emergence of a new clone of serogroup C, serotype 2a (electrophoretic type ET-15), was observed in North America (3). In the province of Quebec in Canada, the situation was considered sufficiently severe to justify a systematic immunisation campaign of 1.6 million children in 1993 (4). In 1996, the incidence was less than 1/100 000 in Quebec as well as in other Canadian provinces and serogroup C accounted only for 38% of isolates compared with 65% in 1992 (5). In Spain, an increase in incidence and case fatality rates was associated with an increase of the phenotype C:2b:P1.2,5. Community vaccination campaigns were conducted in three regions in December 1996 and February 1997. It has been announced that these campaigns will be extended to three other Spanish regions in the forthcoming high incidence season (6).

In this issue of Eurosurveillance, reports from seven countries (Spain, England and Wales, Ireland, Scotland, Greece, France, and Belgium) illustrate the differences in the incidence of reported cases and the distribution of prevalent serogroups and serotypes between European countries.

The reported incidence of meningococcal disease in 1996 varied from less than 1/100 000 in France to 1.3/100 000 in Greece, 2/100 000 in Belgium and up to 4-5/100 000 in the other four countries. Differences in reporting systems probably account for a substantial proportion of these variations. The sensitivity (probability that a meningococcal infection will be notified) and the positive predictive value (PPV) (probability that a notified case is really a meningococcal infection) differ markedly between countries. The PPV is highly dependent on the case definition used for surveillance purposes. As an illustration, notification systems in France and in Spain (7) differ in sensitivity (70% and 93%, respectively) and PPV (91% and 70%) such that, if the two countries had the same real incidence, the reported incidence would be 1.7 times higher in Spain than in France.

Characteristics of the strains isolated in the seven countries also differed:

- England and Wales, Scotland, the Republic of Ireland, and Greece are experiencing an increase in C:2a isolates. In England and Wales, it has been shown that this increase is caused by the ET-15 clone of the ET-37 complex, as in North America (8).

- In Belgium and France, an increase in serogroup B, mainly serotype B:4:P1.4 has been observed. These strains belong to clones of lineage III (1). This situation may have resulted from a southward migration of the clones of lineage III present in the Netherlands since the 1980s (2).

- In Spain, a marked increase of the C:2b:P1.2,5 strains has been observed. It is noteworthy that this phenotype is not really new in Europe and predominated in Scotland in the 1980s. This clone probably belongs to the cluster A4 of meningococci. The same clone complex was also predominant in Greece in the early 1990s, but associated with serogroup B polysaccharide.

These seven countries cannot be considered as representative of the whole of Europe; the prevailing tendency in Europe seems to be an increase in serogroup C. The King's College European Meningitis Surveillance Project, based on reports from national reference laboratories of 24 countries, found that the proportion of isolates of serogroup C rose from 27% in 1995 to 33% in the first six months of 1996 (9). The ET-5 complex (represented mainly by B:15:P1.7,16 and B:4:P1.15) responsible of the major epidemics in Europe in the 1970s and 1980s is, although decreasing, still the most prevalent clone of serogroup B in Scandinavia. As suggested by the rapid decrease in the proportion of isolates of serogroup C observed in France in 1993, in the south of the Republic of Ireland in 1996 or in Canada, epidemics or hyperendemic waves of serogroup C infections seem to be of shorter duration than for serogroup B.

The aim of surveillance is to propose appropriate preventive measures. In some countries, the recent increase in serogroup C infections raised the question of whether vaccination campaigns should be held. Various criteria have been used or proposed for deciding vaccination campaigns during these past years, illustrating the difficulty of such a decision :

  • In the province of Quebec in Canada, vaccination was undertaken when the annual incidence of serogroup C meningococcal disease reached 5/100 000 among people aged 1 to 20 years in two consecutive years with an unusually high attack rate among teenagers and a high case fatality rate (3).
  • In England, no precise threshold for intervention has been determined, but two interventions in community outbreaks were undertaken when attack rates reached >40/100 000 among children 2 to 16 years old (10).
  • Recently, in Spain, a Public Health Commission recommended vaccination if the annual incidence of meningococcal disease exceeded 10 cases per 100 000 people of all ages (5).
  • In the United States, the Advisory Committee on Immunization Practices has proposed an attack rate of, at least, 10 cases of serogroup C meningococcal disease per 100 000 persons during a period of <= 3 months.
    Current WHO guidelines for countries with high rates of meningococcal infection (in sub-Saharan Africa) recommended vaccination if the weekly incidence exceeded 15/100 000 for two consecutive weeks (12).

Development of new vaccines are underway and cost-benefit analyses will be soon needed. These analyses will depend on accurate and timely measurements of disease incidence by the surveillance systems. The comparability of data between European countries is questionable and we need at least a common case definition for surveillance purposes.

We anticipate that genotyping methods will become more and more useful in interpreting surveillance data, indicating a need for close collaboration between national reference laboratories and epidemiological surveillance centres.


References
  1. Caugant DA. Epidémiologie de Neisseria meningitidis. L'analyse des clones. Annales de l'Institut Pasteur/Actualités. 1994; 5: 130-7.
  2. Scholten RJ, Poolman JT, Valkenburg HA, Bijlmer HA, Dankert J, Caugant DA. Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in the Netherlands, 1958-1990. J Infect Dis 1994; 169: 673-6.
  3. Whalen CM, Hockin JC, Ryan A, Ashton F. The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis. JAMA 1995; 273: 390-4.
  4. De Wals P, Dionne M, Douville-Fradet M, Boulianne N, Drapeau J, De Serres G. Impact of a mass immunization campaign against serogroup C meningococcus in the Province of Quebec, Canada. Bull World Health Organ 1996; 74: 407-11.
  5. Deeks S, Kertesz D. Surveillance of invasive meningococcal disease in Canada, 1995-6. Can Commun Dis Rep 1997; 23: 121-5.
  6. De Mateo S. Public Health Commission response to meningococcal disease in Spain. Eurosurveillance Weekly. 260697. (http://www.eurosurv.org)
  7. Ladrero MO, Martinez Navarro JF. Evaluacion de la vigilancia de infeccion meningococica en el sistema de enfermedades de declaration obligatoria en la Comunidad Autonoma de Aragon, 1994. Boletín Epidemiologico Semanal 1995; 3: 189-91.
  8. Kaczmarski EB. Meningococcal disease in England and Wales. 1995. Commun Dis Rep CDR Rev 1997; 7: R55-9.
  9. Noah N, Connolly M. Surveillance of bacterial meningitis in Europe 1995. London: King's College 1996.
  10. Stuart JM, Monk PN, Lewis DA, Constantine C, Kaczmarski EB, Cartwright KA. Management of clusters of meningococcal disease. Commun Dis Rep CDR Rev 1997; 7: R3-5.
  11. Advisory Committee on Immunisation Practices. Control and prevention of serogroup C meningococcal disease: evaluation and management of outbreaks. MMWR Morb Mortal Wkly Rep 1997; 46(RR-5): 13-21.
  12. World Health Organization. Control of epidemic meningococcal infection: WHO practical guidelines. Geneva: WHO, 1995.


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